1.Exploration of Pulmonary Vascular Remodeling Improvement in Rats at Different Stages of Chronic Obstructive Pulmonary Disease by Qibai Pingfei Capsules Based on TLR4/NF-κB Signaling Pathway
Lu ZHANG ; Li FANG ; Shuyu XU ; Xue LIANG ; Jie ZHU ; Xiangli TONG ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):48-56
ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease (COPD) and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley (SD) rats were randomly divided into a normal group, an early COPD model group, an advanced COPD model group, an early-intervention high-dose group, a late-intervention high-dose group, an early-intervention low-dose group, a late-intervention low-dose group, an early-intervention pyrrolidine dithiocarbamate (PDTC) group, and a late-intervention PDTC group, with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide(LPS), and a rat model of advanced COPD was constructed by using airway infusion with LPS, cigarette smoke, and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment, smoked for 1 h per day, and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups, rats were given 1 g·kg-1 and 250 mg·kg-1 Qibai Pingfei capsules, respectively by gavage, and in PDTC groups, rats were given 100 mg·kg-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin(HE)staining. Collagen deposition in lung tissues was examined by Masson staining, and the levels of inflammatory factors including interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA). The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining, and the protein expression of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-κB(NF-κB), TNF-α, vascular endothelial-cadherin(VE-cadherin), α-smooth muscle actin(α-SMA), and platelet endothelial cell adhesion molecule-1(CD31) was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group, the model group showed significantly decreased forced expiratory volume in 0.3 s (FEV0.3), forced vital capacity (FVC), and FEV0.3/FVC ratio related to lung function (P<0.05), thickening of pulmonary vasculature, increased collagen deposition in the lungs, and enhanced mean pulmonary arterial pressure and expression levels of IL-6, IL-1β, and TNF-α (P<0.05). Additionally, the model group also exhibited increased numbers of macrophages, lymphocytes, and neutrophils (P<0.05), significantly higher protein expression of TLR4, MyD88, NF-κB, TNF-α, and α-SMA (P<0.05), and significantly lower protein expression of VE-cadherin and CD31 (P<0.05). Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group (P<0.05), with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6, IL-1β, and TNF-α (P<0.05) and decreased numbers of macrophages, lymphocytes, and neutrophils (P<0.05), as well as reduced protein expression of TLR4, MyD88, NF-κB, TNF-α, and α-SMA (P<0.05) and elevated protein expression of VE-cadherin and CD31 (P<0.05) in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway, thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.
2.Surveillance results of intestinal helminth infections in Lunan area of Shandong Province from 2016 to 2023
Wenxiang LYU ; Na WANG ; Yongbin WANG ; Cancan BU ; Yuejin LI ; Longjiang WANG ; Xiangli KONG ; Benguang ZHANG ; Ge YAN ; Yan XU
Chinese Journal of Endemiology 2025;44(7):579-584
Objective:To understand the status of intestinal helminth infections in Lunan area of Shandong Province (Jining City, Rizhao City, Linyi City, Heze City, and Zaozhuang City), and provide scientific basis for formulating parasitic disease prevention and control strategies.Methods:From 2016 to 2023, a stratified sampling method was used to conduct surveillance in 33 counties (cities, districts, hereinafter referred to as counties) in Lunan area of Shandong Province. Each county was divided into five areas (east, south, west, north, and center), with one administrative village (community) selected from each area. And ≥200 permanent residents (aged ≥3 years old, having lived locally for ≥6 months) were sampled from each village (community), and one stool sample was collected from each participant. The Kato-Katz method (two slides per sample) was used for parasite detection, and the results were analyzed.Results:From 2016 to 2023, a total of 49 436 people were surveyed, including 23 861 males and 25 575 females, with an age range of 3 - 105 years old. The testing identified 687 intestinal helminth infections, with an overall infection rate of 1.39%. The predominant infection was whipworm (582 cases), with an infection rate of 1.18%; followed by roundworm and hookworm, with infection rates of 0.13% (62 cases) and 0.05% (23 cases) respectively; other types of helminths ( Clonorchis sinensis and pinworm) totaled 20 cases, with an infection rate of 0.04%. From 2016 to 2023, the annual intestinal helminth infection rates were 2.76% (201/7 292), 0.90% (56/6 327), 0.84% (52/6 200), 1.70% (124/7 282), 1.23% (88/7 133), 1.45% (104/7 150), 0.34% (17/5 058), and 1.46% (45/3 084), showing an overall downward trend (χ 2trend = 42.40, P < 0.001). The ≥60 age group had the highest intestinal helminth infection rate (2.39%, 323/13 489), while the 30 - 39 age group had the lowest rate (0.68%, 48/7 016). There was statistically significant difference in infection rates among different age groups (χ 2 = 172.25, P < 0.001). There was no statistically significant difference in infection rates between genders (χ 2 = 0.03, P = 0.862). Farmers had the highest infection rate (1.69%, 560/33 118), with statistically significant differences among different occupational groups (χ 2 = 64.88, P < 0.001). Those with primary school education or below had the highest infection rate (1.82%, 445/24 469), with statistically significant differences among different education levels (χ 2 = 64.93, P < 0.001). Conclusions:In Lunan area of Shandong Province, whipworm is the predominant intestinal helminth infection, with elderly people being the high-risk group. Although the intestinal helminth infection rate in this region remains at a low level, there is still a risk of transmission. Continuous surveillance is needed, along with strengthened prevention and control measures for key populations.
3.Membrane induction technique to treat chronic bone infection after internal fixation of intertrochanteric fracture in adults
Yunfei XIE ; Xiaotian LU ; Yitong SU ; Xiangli LUO ; Meng LI
Chinese Journal of Orthopaedic Trauma 2025;27(3):197-203
Objective:To explore the clinical efficacy of membrane induction technique in the treatment of chronic bone infection after internal fixation of intertrochanteric fracture in adults.Methods:The data were retrospectively analyzed of the 15 adult patients who had been treated for chronic bone infection after internal fixation of intertrochanteric fracture at Department of Traumatic Orthopaedics Ⅱ, Gansu Provincial People's Hospital from May 2019 to May 2022. There were 13 males and 2 females with an age of (55.8±2.6) years. By the Cierny-Mader anatomical classification, 6 cases were type Ⅲ and 9 cases type Ⅳ; by the physiological classification, 10 cases were type A and 5 cases type B. Course of bone infection was (22.1±8.1) months. All patients were treated by membrane induction technique in 2 stages. In the first stage, antibiotic bone cement was implanted after debridement into the defects [(4.50±0.54) cm in length] followed by temporary fixation of broken ends of the fracture. After 6 to 8 weeks when infection was controlled, the second stage repair and reconstruction of bone defects was carried out. Infection control, complications, bone healing time, and Samantha X-ray bone healing score, visual analogue scale (VAS) at standing, Sanders hip score and Paley score for bone defect healing at the last follow-up were recorded.Results:The 15 patients were followed up for (27.5±2.5) months. Infection recurred after the first-stage operation in 2 cases, but was effectively controlled after debridement and follow-up observed no recurrence. Follow-up showed no such complications as donor site infection, deformation or collapse of the bone reconstructed, limb shortening, re-fracture or internal fixation failure in the 15 patients who achieved bony union after (10.3±2.1) months. At the last follow-up, the Samantha X-ray score was 6.0(5.0, 6.0) points and VAS at standing 1.0(1.0, 3.0) point for the 15 patients; by Sanders hip score, the hip function was rated as excellent in 10 cases and as fine in 5 cases; by Paley score for bone defect healing, the efficacy was rated as excellent in 7 cases, as good in 2 cases and as fair in 6 cases.Conclusion:In the treatment of chronic bone infection after internal fixation of intertrochanteric fracture in adults, membrane induction technique can effectively control infection and improve the hip function of the affected limb, leading to good clinical efficacy.
4.The Influencing Factors of Delayed Onset of Intrapartum Fever Related to In-trathecal Labor Analgesia and its Impact on Maternal and Neonatal Outcomes
Fei JIA ; Liang LING ; Bo LIU ; Chunping LI ; Huiru LI ; Xiangli SHEN ; Mengjiao WANG ; Dan ZHANG ; Jian ZHANG
Journal of Practical Obstetrics and Gynecology 2025;41(2):169-173
Objective:To investigate the factors influencing the delayed onset of intrapartum fever following epidural labor analgesia and their impact on maternal and neonatal outcomes.Methods:Select parturients who experienced intrapartum fever following labor analgesia(T≥38.0℃,age≥18 years,singleton pregnancy,ASA classification Ⅱ)between January 1,2021,and December 31,2023.Group them based on the median time of intra-partum fever onset after labor analgesia:those with onset times less than the median were classified as the ear-ly-onset fever group,and those with onset times greater than the median were classified as the late-onset fever group.Using univariate and multivariate Logistic regression analysis to explore factors influencing the delay in in-trapartum fever onset and the pregnancy outcomes of the mothers and newborns in both groups.Results:A total of 253 parturients were included,and the time range of onset of intrapartum fever following epidural labor analgesi-a was 1.83-28.42 hours,with a median fever onset time of 8.00 hours.There were 126 cases in the early-onset group and 127 in the late-onset group.Multivariate Logistic regression analysis indicated that primiparous women,artificial membrane rupture,and neonatal birth weight were independent risk factors for delayed fever onset(OR>1,P<0.05),whereas the administration of oxytocin prior to labor analgesia was found to be a protective factor(OR<1,P<0.05).The late-onset group exhibited higher levels of white blood cells(WBC),C-reactive pro-tein,longer hospital stays,higher hospitalization costs,greater diagnosis rates of chorioamnionitis,higher NICU ad-mission rates,as well as a higher incidence of neonatal pneumonia,for newborns compared to the early-onset group(P<0.05).Conclusions:Primiparous women,artificial membrane rupture,and higher neonatal birth weight may be associated with delayed onset of intrapartum fever,while oxytocin administration prior to labor analgesia may offer some protective benefit.The later the onset of intrapartum fever,the worse the clinical outcomes for both mother and infants.
5.Research progress of SNARE complex in autophagy and related diseases
Caiyin LI ; Yuan LIU ; Roujia GUO ; Jingjing BU ; Xiangli YAN ; Yucheng LI
Chinese Journal of Pathophysiology 2025;41(1):188-194
Autophagy is a conserved physiological phenomenon commonly found in all eukaryotic cells,which promotes cell survival by degrading intracellular proteins and organelles during starvation or nutrient deficiency.Dysfunc-tion autophagy is closely related to various diseases.Soluble N-elthylmaleimide-sensitive factor attachment protein recep-tor(SNARE)complex is a protein complex that mediates membrane fusion and plays a key role in the fusion process of au-tophagosomes and lysosomes.The aberrant assembly of the SNARE complex results in the arrest of autophagic flow,there-by leading to cellular dysfunction and the occurrence of diseases.In this review,we summarized the roles of SNARE pro-teins in the autophagosome-lysosome fusion and the latest research in related diseases,providing a reference for studying the mechanism of autophagy and diseases targeting the SNARE complex.
6.The value of machine learning models based radiomics for predicting high-risk molecular subtypes of lower-grade gliomas
Xiangli YANG ; Guoqiang YANG ; Wenju NIU ; Xueting LI ; Yan TAN ; Xiaochun WANG ; Lizhi XIE ; Hui ZHANG
Chinese Journal of Radiology 2025;59(8):909-916
Objective:To evaluate the clinical utility of machine learning model based radiomics in predicting high-risk molecular subtypes of lower-grade gliomas(LrGGs).Methods:This was a cross-sectional study. A total of 287 patients diagnosed with LrGGs in the First Hospital of Shanxi Medical University, Shanxi Provincial People′s Hospital, and the Third Hospital of Shanxi Medical University from January 2011 to September 2023 were retrospectively collected, including 166 males and 121 females; 114 cases of high-risk molecular subtypes and 173 cases of non-high-risk molecular subtypes. All patients were divided into 201 cases in the training set and 86 cases in the test set according to 7∶3 in simple randomized grouping method. All patients underwent contrast-enhanced T 1WI (CE-T 1WI) and T 2-weighted fluid-attenuated inversion recovery sequence imaging (T 2-FLAIR), and the imaging features of high-risk and non-high-risk molecular subtypes were analyzed. Analysis of variance, recursive feature elimination, and Kruskal-Wallis were used for radiomics feature screening, and a support vector machine (SVM) classifier was used to construct a radiomics-based classifier model. Univariate and multivariate logistic regression were used to analyze clinical variables independently influencing high-risk molecular subtypes of LrGGs to construct a clinical model; a combined model was developed by integrating radiomics labels and clinical variables. Receiver operating characteristic curve and area under the curve (AUC), calibration curve, and decision curve were used to compare the predictive performance of different models. Results:The patient′s age ( OR=1.042, 95% CI 1.018-1.068, P=0.001), pathological grade ( OR=2.270, 95% CI 1.212-4.311, P=0.011), MGMT methylation status ( OR=0.456, 95% CI 0.238-0.866, P=0.017), and ependymal involvement ( OR=7.335, 95% CI 2.929-18.370, P<0.001) were independent influencing factors for the high-risk molecular subtype of LrGGs, and a clinical model was developed based on these factors. An SVM model was constructed based on 12 radiomics features (3 radiomics features based on CE-T 1WI and 9 radiomics features based on T 2-FLAIR). The radiomics score of the probability output by the SVM model was combined with age, pathological grade, MGMT methylation status, and ependymal involvement to develop a combined model. The AUC values of the SVM model for predicting the high-risk molecular subtype of LrGGs were 0.824 and 0.859 in the training set and test set, respectively; the AUC values of the clinical model in the training set and test set were 0.759 and 0.721, respectively; and the AUC values of the combined model in the training set and test set were 0.823 and 0.815, respectively. The combined model had a high clinical net benefit. Conclusion:The machine learning MRI radiomics model can preoperatively predict high risk molecular subtypes of LGGrs, assist in individualized treatment decisions.
7.FGF21 ameliorates severe acute pancreatitis-associated acute lung injury in rats by modulating autophagy
Chenglong CAO ; Ling ZHANG ; Xiangli MA ; Shixian LIU ; Yijing LIU ; Peiwu LI
Chinese Journal of Emergency Medicine 2025;34(5):669-675
Objective:To explore the role of fibroblast growth factor 21 (FGF21) in rats with severe acute pancreatitis-associated acute lung injury (SAP-ALI) and its related molecular mechanisms.Methods:Twenty-four healthy male SD rats were randomly divided into 4 groups (random number, n=6 per group): Control group, SAP group, FGF21 intervention group (SAP+FGF21 group), and autophagy inhibitor group (SAP+FGF21+3-MA group). The SAP model was established by retrograde injection of 3.5% sodium taurocholate into the pancreatic duct. In SAP+FGF21 group, FGF21 10 mg/kg was intraperitoneally injected at 1 hour before modeling. In SAP+FGF21+3-MA group, FGF21 10 mg/kg and 3-MA 20 mg/kg were intraperitoneally injected at 1 h before modeling. Serum amylase activity was detected by biochemical kit. Plasma levels of tumor necrosis factor alpha (TNF-α) and FGF21 were detected by ELISA. HE staining was used to observe the pathological changes of pancreas and lung tissues. Immunofluorescence was used to detect the protein level of FGF21 in lung tissue. Western blot was used to detect the expression levels of autophagy-related proteins in lung tissue. Autophagosomes in lung tissue were observed by electron microscopy. Results:Compared with the Control group, the plasma and lung tissue FGF21 levels in SAP group were significantly decreased (both P<0.001) , severe pancreatic and lung tissue damage, and elevated plasma TNF-α levels ( P<0.001). Western Blot and transmission electron microscopy showed that: The expression of LC3Ⅱ/Ⅰ in lung tissue of SAP group was down-regulated [(0.912±0.052) vs. (0.700±0.135), P<0.001], and P62 protein level was up-regulated [(0.475±0.068) vs. (0.687±0.070), P<0.001] , and reduced autophagosome counts in the SAP group. In contrast, the SAP+FGF21 group showed elevated FGF21 levels (both P<0.01), attenuated pancreatic and lung injury ( P<0.001), decreased TNF-α levels [(280.10±49.36) pg/mL vs. (86.32±66.00) pg/mL, P<0.001]. Lung tissue of LC3 Ⅱ/Ⅰ levels increase [(0.700±0.135) vs. (0.853±0.073), P<0.01], P62 protein levels cut [(0.687±0.070) vs. (0.538±0.030), P<0.01] ], and increased autophagosomes and autolysosomes under electron microscopy. Compared with SAP+FGF21 group, the expression levels of FGF21 in plasma and lung tissue in SAP+FGF21+3-MA group were not significantly changed, and the level of autophagy was decreased. Pancreas and lung tissue injury was severe ( P<0.001), Plasma TNF-α level obviously higher [(86.32±66.00) pg/mL vs. (212.90±11.56) pg/mL, P<0.05]. Conclusion:FGF21 may play a protective role in SAP-ALI by up-regulating the level of autophagy.
8.Discovery of bioactive polycyclic polyprenylated acylphloroglucinol from Hypericum patulum that protects against hepatic ischemia/reperfusion injury.
Bo TAO ; Xiangli ZHAO ; Zhengyi SHI ; Jie LI ; Yulin DUAN ; Xiaosheng TAN ; Gang CHEN ; Changxing QI ; Yonghui ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(9):1104-1110
Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control*
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Animals
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Hypericum/chemistry*
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Phloroglucinol/administration & dosage*
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Mice
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Humans
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Male
;
Liver/blood supply*
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Apoptosis/drug effects*
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Molecular Structure
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Protective Agents/pharmacology*
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Hepatocytes/drug effects*
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Mice, Inbred C57BL
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Liver Diseases/drug therapy*
9.Association of MICA gene polymorphisms and SNP loci with susceptibility to rosacea.
Xiangli YIN ; Quan ZHU ; Ji LI ; Yizhou ZOU ; Qizhi LUO
Journal of Central South University(Medical Sciences) 2025;50(3):319-330
OBJECTIVES:
The major histocompatibility complex class I chain-related gene A (MICA), a component of the human leukocyte antigen (HLA) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among MICA gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism.
METHODS:
Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. MICA genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of MICA alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined.
RESULTS:
Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified MICA alleles. The most common alleles in the rosacea group were MICA*010:01, MICA*008:04, and MICA*019:01. The frequencies of MICA*002:01 and MICA*027 were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and MICA*010:01 were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all P<0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of MICA-A4 and MICA-A9 were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas MICA-A6 was higher (10.12% vs 4.03%; all P<0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C36+M129+K173+G206+W210+S215) and Type II (Y36+V129+E173+S206+R210+T215). Type I MICA variants were significantly associated with rosacea susceptibility.
CONCLUSIONS
MICA gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the MICA gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans
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Polymorphism, Single Nucleotide
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Histocompatibility Antigens Class I/genetics*
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Rosacea/genetics*
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Genetic Predisposition to Disease/genetics*
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Female
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Male
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Adult
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Middle Aged
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Genotype
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Alleles
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Gene Frequency
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Haplotypes
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Case-Control Studies
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Aged
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High-Throughput Nucleotide Sequencing
10.Improvement effect of lovastatin on hyperlipidemia-induced liver injury in rats and its mechanism
Yi ZHAO ; Bing ZHOU ; Huirui QIU ; Xuan LI ; Xiangli CUI
Journal of Jilin University(Medicine Edition) 2025;51(5):1155-1164
Objective:To investigate the protective effect of lovastatin on liver injury in the rats induced by hyperlipidemia,and to elucidate its possible mechanism.Methods:Fifteen SD rats were randomly divided into control group,hyperlipidemia model group,and lovastatin group,with 5 rats in each group.The rats in control group were fed with standard diet,while the rats in hyperlipidemia model group and lovastatin group were fed high-fat diet for 12 weeks.Starting from the 8th week,the rats were administered treatments via gavage once a day for 4 weeks:the rats in lovastatin group received 2 mng·kg-1 lovastatin,while the rats in control group and hyperlipidemia model group received an equal volume of normal saline.The body weights of the rats in various groups were measured at weeks 1,8,9,10,11,and 12 after the experiment began;the histopathology of liver tissue of the rats in various groups was observed using HE staining;the serum levels of total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),malondialdehyde(MDA),as well as the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),and the levels of interleukin-2(IL-2),interleukin-6(IL-6),interleukin-12(IL-12),and tumor necrosis factor-a(TNF-α)of the rats in various groups were detected using commercial kits;the composition of the gut microbiota of the rats in various groups was analyzed by 16S rRNA sequencing.Results:Compared with control group,the body weight of the rats in hyperlipidemia model group was significantly increased from the 8th week of high-fat diet feeding(P<0.05 or P<0.01 or P<0.001).Compared with hyperlipidemia model group,the body weight of the rats in lovastatin group was significantly decreased at weeks 11 and 12(P<0.05).Compared with control group,the livers of the rats in hyperlipidemia model group appeared rough,pale,enlarged,with blunt edges,and had a granular and greasy texture.Compared with hyperlipidemia model group,the livers of the rats in lovastatin group were light brownish-red,soft,with slightly blunt edges,reduced volume,and less granularity and greasiness.Compared with control group,the liver cells of the rats in hyperlipidemia model group were swollen and disorganized,with pyknotic nuclei,extensive inflammatory cell infiltration,and numerous vacuolar degenerations.Compared with hyperlipidemia model group,the rats in lovastatin group showed significantly reduced hepatocyte swelling and degeneration,more orderly and intact liver cell arrangement,decreased inflammatory cell infiltration,and reduced vacuolar degeneration.Compared with control group,the serum levels of TC,TG,and LDL-C of the rats in hyperlipidemia model group were significantly increased(P<0.05),and the serum HDL-C level was decreased(P<0.05).Compared with hyperlipidemia model group,the serum levels of TC,TG,and LDL-C of the rats in lovastation group were significantly decreased(P<0.05),and the serum HDL-C level was increased(P<0.05).Compared with control group,the serum MDA levels and the ALT and AST activities of the rats in hyperlipidemia model group were significantly increased(P<0.05),and the SOD and GSH-Px activities were significantly decreased(P<0.05).Compared with hyperlipidemia model group,the serum MDA levels and ALT and AST activities of the rats in lovastatin group were decreased(P<0.05),and the SOD and GSH-Px activities were increased(P<0.05).Compared with control group,the serum levels of IL-2,IL-6,IL-12,and TNF-α of the rats in hyperlipidemia model group were significantly increased(P<0.05).Compared with hyperlipidemia model group,the serum levels of IL-2,IL-6,IL-12,and TNF-α of the rats in lovastatin group were significantly decreased(P<0.05).Compared with control group,the ACE and Chao1 indexes of the rats in hyperlipidemia model group were significantly decreased(P<0.05).Compared with hyperlipidemia model group,the ACE and Chao1 indexes of the rats in lovastatin group were significantly increased(P<0.05 or P<0.01).Compared with control group,the relative abundances of Firmicutes and Proteobacteria of the rats in hyperlipidemia model group were significantly increased(P<0.001),and the relative abundances of Bacteroidetes and Actinobacteria were decreased(P<0.001).Compared with hyperlipidemia model group,the relative abundances of Firmicutes and Proteobacteria of the rats in lovastatin group were significantly decreased(P<0.05 or P<0.01),while the relative abundances of Bacteroidetes and Actinobacteria showed no significant changes.Compared with control group,the relative abundance of Lactobacillus of the rats in hyperlipidemia model group was significantly decreased(P<0.001),and the relative abundances of Bacteroides,Desulfovibrio,and Clostridium were significantly increased(P<0.01 or P<0.001).Compared with hyperlipidemia model group,the relative abundance of Lactobacillus of the rats in lovastatin group showed no significant change but the relative abundances of Bacteroides,Desulfovibrio,and Clostridium were significantly decreased(P<0.05 or P<0.01 or P<0.001).Conclusion:Lovastatin ameliorates liver injury induced by hyperlipidemia,and the mechanism may be related to its ability to improve gut microbiota composition and inhibit oxidative stress and inflammatory damage.

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