1.Molecular expression and pathological morphologic changes of extraocular muscle in concomitant exotropia
Xiaorui ZHOU ; Zhibin WANG ; Yu DI
International Eye Science 2025;25(1):55-58
Strabismus, a common ocular condition, arises from an imbalance in the extraocular muscle force and deviation of the visual axis due to various factors. Concomitant strabismus is the predominant form of exotropia, with its pathogenesis believed to be associated with hereditary factors, abnormal eye accommodation function, and anomalies in binocular anatomy. Surgical intervention is often necessary for aligning the visual axes of both eyes and facilitating the recovery and establishment of stereoscopic vision. Despite this, the etiology of concomitant exotropia remains incompletely understood. This review consolidates recent research on aberrant molecular expression and pathological morphological changes within extraocular muscles affected by concomitant exotropia, offering insights into disease causation at molecular and pathological levels to underpin future preventive measures and clinical interventions. The discussion encompasses histological changes observed under electron microscopy as well as the impact of heavy chain protein, satellite cells, cadherin, growth factors on extraocular muscle protein expression.
2.Analysis of major food consumption frequencies among children aged 6-17 years in China
Chinese Journal of School Health 2025;46(4):494-499
Objective:
To analyze the consumption frequency of major foods among Chinese children aged 6-17 years old, and to provide a basis for optimizing the dietary structure of children in China.
Methods:
Using data from the China Nutrition and Health System Survey and Application Program for Children 0-18 years old, 56 734 children aged 6-17 years old from North, Norththeast East, Central, South, Southwest and Northwest seven regions in China were selected for the study using stratified cluster random sampling from 2019 to 2021. A food frequency questionnaire was used to investigate the intake frequency of eight food groups in a month, including fresh vegetables, fresh fruits, livestock and poultry meats, aquatic products, eggs, dairy products, legumes, and cereals and potatoes. The foods were grouped according to whether they met the recommended intake criteria outlined in the Dietary Guidelines for Chinese Residents 2022. The〖KG*2〗χ2 test was used to compare the differences in the proportion of childrens intake frequency of each food group meeting the standard in different regions and age groups.
Results:
The proportions of Chinese children aged 6-17 years who consumed fresh vegetables and cereals and potatoes ≥3 times/d were 12.1% and 67.2%, respectively. The proportions of children who consumed fresh fruits, livestock and poultry meats, eggs and dairy products ≥1 time/d were 50.8%, 58.8%, 36.0% and 54.3%, respectively. The proportion of legumes consumed ≥4 times/week was 37.4%, and the proportion of aquatic products consumed ≥2 times/week was 39.7%. Fresh vegetables (5.5%), fresh fruits (33.1%), and dairy products (36.4%) had the lowest frequency of meeting the recommended standards in South China, and aquatic products (27.4%) and eggs (21.1%) had the lowest frequency of meeting the recommended standards in Northwest (P<0.008 3).
Conclusion
The overall intake frequency of fresh vegetables, fresh fruits, legumes, and dairy products are insufficient among Chinese children, with significant regional variations.
3.Shenqi Dihuang Decoction Improves Renal Function in Mouse Model of Diabetic Kidney Disease by Inhibiting Arachidonic Acid-related Ferroptosis Via ACSL4/LPCAT3/ALOX15 Axis
Yuantao WU ; Zhibin WANG ; Xinying FU ; Xiaoling ZOU ; Wenxiao HU ; Yixian ZOU ; Jun FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):140-149
ObjectiveTo investigate the therapeutic effects and mechanism of Shenqi Dihuang decoction (SQDHD) on diabetic kidney disease (DKD), with a focus on its impact on arachidonic acid-related ferroptosis. MethodsSixty C57BL/6 mice were allocated into a normal group (n=10) and a modeling group (n=50), with 43 mice successfully modeled. The successfully modeled mice were further allocated into model, low-, medium-, and high-dose (4.68, 9.36, and 18.72 g·kg-1, respectively) SQDHD, and dapagliflozin (0.13 mg·kg-1) groups. The drug treatment groups were administrated with corresponding agents by gavage, and the normal and model groups were administrated with equal volumes of normal saline by gavage. An electronic balance and a glucometer were used to monitor the body weight and fasting blood glucose level from the tail tip, respectively. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured by enzyme-linked immunosorbent assay (ELISA). Histopathological changes in the renal tissue were assessed by hematoxylin-eosin staining, Masson staining, and periodic acid-Schiff (PAS) staining. The fluorescence intensity of reactive oxygen species (ROS) in frozen sections was observed by an inverted fluorescence microscope to evaluate the levels of ferrous ions (Fe2+) and lipid peroxidation in the renal tissue. Immunofluorescence staining of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the renal tissue was performed to detect their localization and expression. Western blot was employed to assess the expression levels of key ferroptosis proteins such as GPX4 and cystine/glutamate antiporter (xCT), as well as the arachidonic acid metabolic pathway-related proteins, including ACSL4, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate 15-lipoxygenase (ALOX15). Real-time PCR was employed to measure the mRNA levels of key ferroptosis proteins, including solute carrier family 7 member 11 (SLC7A11) and GPX4, as well as arachidonic acid metabolism-related factors (ACSL4, LPCAT3, and ALOX15) in the renal tissue. ResultsCompared with the normal group, DKD model mice exhibited a decrease in body weight (P<0.01), increases in levels of blood glucose (P<0.01), 24-hour urinary protein, Scr, and BUN (P<0.01), along with severe pathological changes, such as mesangial cell proliferation, basement membrane thickening, tubular atrophy, and interstitial inflammatory cell infiltration. In addition, the modeling elevated the levels of Fe2+, MDA, LPO, and ROS (P<0.01), lowered the GPX4 and xCT levels (P<0.01), raised the ACSL4, LPCAT3, and ALOX15 levels (P<0.01), down-regulated the mRNA levels of GPX4 and SLC7A11 (P<0.01), and up-regulated the mRNA levels of ACSL4, LPCAT3, and ALOX15 (P<0.01) in the renal tissue. Compared with the model group, low-, medium-, and high-dose SQDHD groups and the dapagliflozin group showed an increase in body weight (P<0.01), decreases in levels of blood glucose (P<0.01), 24-hour urinary protein, and Scr (P<0.01), alleviated pathological changes in glomeruli and tubules, and reduced degree of glomerular and tubular fibrosis. The high-dose SQDHD group and the dapagliflozin group showed reductions in Fe2+, MDA, LPO, and ROS levels (P<0.01). The medium- and high-dose SQDHD groups and the dapagliflozin group exhibited increased levels of GPX4 and xCT (P<0.01), decreased levels of ACSL4, LPCAT3, and ALOX15 (P<0.05, P<0.01), and down-regulated mRNA levels of ACSL4, LPCAT3, and ALOX15 (P<0.01). ConclusionSQDHD ameliorates DKD by inhibiting ferroptosis potentially by reducing iron ion levels, inhibiting lipid peroxidation, up-regulating GPX4 expression, and down-regulating ACSL4 expression. This study provides new insights and a theoretical basis for the treatment of DKD with traditional Chinese medicine and identifies potential targets for developing novel therapeutics for DKD.
4.Shenqi Dihuang Decoction Improves Renal Function in Mouse Model of Diabetic Kidney Disease by Inhibiting Arachidonic Acid-related Ferroptosis Via ACSL4/LPCAT3/ALOX15 Axis
Yuantao WU ; Zhibin WANG ; Xinying FU ; Xiaoling ZOU ; Wenxiao HU ; Yixian ZOU ; Jun FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):140-149
ObjectiveTo investigate the therapeutic effects and mechanism of Shenqi Dihuang decoction (SQDHD) on diabetic kidney disease (DKD), with a focus on its impact on arachidonic acid-related ferroptosis. MethodsSixty C57BL/6 mice were allocated into a normal group (n=10) and a modeling group (n=50), with 43 mice successfully modeled. The successfully modeled mice were further allocated into model, low-, medium-, and high-dose (4.68, 9.36, and 18.72 g·kg-1, respectively) SQDHD, and dapagliflozin (0.13 mg·kg-1) groups. The drug treatment groups were administrated with corresponding agents by gavage, and the normal and model groups were administrated with equal volumes of normal saline by gavage. An electronic balance and a glucometer were used to monitor the body weight and fasting blood glucose level from the tail tip, respectively. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured by enzyme-linked immunosorbent assay (ELISA). Histopathological changes in the renal tissue were assessed by hematoxylin-eosin staining, Masson staining, and periodic acid-Schiff (PAS) staining. The fluorescence intensity of reactive oxygen species (ROS) in frozen sections was observed by an inverted fluorescence microscope to evaluate the levels of ferrous ions (Fe2+) and lipid peroxidation in the renal tissue. Immunofluorescence staining of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the renal tissue was performed to detect their localization and expression. Western blot was employed to assess the expression levels of key ferroptosis proteins such as GPX4 and cystine/glutamate antiporter (xCT), as well as the arachidonic acid metabolic pathway-related proteins, including ACSL4, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and arachidonate 15-lipoxygenase (ALOX15). Real-time PCR was employed to measure the mRNA levels of key ferroptosis proteins, including solute carrier family 7 member 11 (SLC7A11) and GPX4, as well as arachidonic acid metabolism-related factors (ACSL4, LPCAT3, and ALOX15) in the renal tissue. ResultsCompared with the normal group, DKD model mice exhibited a decrease in body weight (P<0.01), increases in levels of blood glucose (P<0.01), 24-hour urinary protein, Scr, and BUN (P<0.01), along with severe pathological changes, such as mesangial cell proliferation, basement membrane thickening, tubular atrophy, and interstitial inflammatory cell infiltration. In addition, the modeling elevated the levels of Fe2+, MDA, LPO, and ROS (P<0.01), lowered the GPX4 and xCT levels (P<0.01), raised the ACSL4, LPCAT3, and ALOX15 levels (P<0.01), down-regulated the mRNA levels of GPX4 and SLC7A11 (P<0.01), and up-regulated the mRNA levels of ACSL4, LPCAT3, and ALOX15 (P<0.01) in the renal tissue. Compared with the model group, low-, medium-, and high-dose SQDHD groups and the dapagliflozin group showed an increase in body weight (P<0.01), decreases in levels of blood glucose (P<0.01), 24-hour urinary protein, and Scr (P<0.01), alleviated pathological changes in glomeruli and tubules, and reduced degree of glomerular and tubular fibrosis. The high-dose SQDHD group and the dapagliflozin group showed reductions in Fe2+, MDA, LPO, and ROS levels (P<0.01). The medium- and high-dose SQDHD groups and the dapagliflozin group exhibited increased levels of GPX4 and xCT (P<0.01), decreased levels of ACSL4, LPCAT3, and ALOX15 (P<0.05, P<0.01), and down-regulated mRNA levels of ACSL4, LPCAT3, and ALOX15 (P<0.01). ConclusionSQDHD ameliorates DKD by inhibiting ferroptosis potentially by reducing iron ion levels, inhibiting lipid peroxidation, up-regulating GPX4 expression, and down-regulating ACSL4 expression. This study provides new insights and a theoretical basis for the treatment of DKD with traditional Chinese medicine and identifies potential targets for developing novel therapeutics for DKD.
5.Endovascular Treatment for Acute Posterior Circulation Tandem Lesions: Insights From the BASILAR and PERSIST Registries
Wei LI ; Mohamed F. DOHEIM ; Zhongming QIU ; Tan WANG ; Zhibin CHEN ; Wenjie ZI ; Qingwu YANG ; Haitao GUAN ; Hongyu QIAO ; Wenhua LIU ; Wei HU ; Xinfeng LIU ; Jinbo HUANG ; Zhongkui HAN ; Zhonglun CHEN ; Zhenqiang ZHAO ; Wen SUN ; Raul G. NOGUEIRA
Journal of Stroke 2025;27(1):75-84
Background:
and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT.
Methods:
Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery.
Results:
A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24).
Conclusion
Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.
6.Endovascular Treatment for Acute Posterior Circulation Tandem Lesions: Insights From the BASILAR and PERSIST Registries
Wei LI ; Mohamed F. DOHEIM ; Zhongming QIU ; Tan WANG ; Zhibin CHEN ; Wenjie ZI ; Qingwu YANG ; Haitao GUAN ; Hongyu QIAO ; Wenhua LIU ; Wei HU ; Xinfeng LIU ; Jinbo HUANG ; Zhongkui HAN ; Zhonglun CHEN ; Zhenqiang ZHAO ; Wen SUN ; Raul G. NOGUEIRA
Journal of Stroke 2025;27(1):75-84
Background:
and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT.
Methods:
Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery.
Results:
A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24).
Conclusion
Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.
7.Endovascular Treatment for Acute Posterior Circulation Tandem Lesions: Insights From the BASILAR and PERSIST Registries
Wei LI ; Mohamed F. DOHEIM ; Zhongming QIU ; Tan WANG ; Zhibin CHEN ; Wenjie ZI ; Qingwu YANG ; Haitao GUAN ; Hongyu QIAO ; Wenhua LIU ; Wei HU ; Xinfeng LIU ; Jinbo HUANG ; Zhongkui HAN ; Zhonglun CHEN ; Zhenqiang ZHAO ; Wen SUN ; Raul G. NOGUEIRA
Journal of Stroke 2025;27(1):75-84
Background:
and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT.
Methods:
Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery.
Results:
A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24).
Conclusion
Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.
8.New interpretation of the theoretical connotation of the correspondence between prescription and syndrome from the longitudinal perspective of"traditional Chinese medicine state"
Shijie QIAO ; Chao FU ; Ziyao CAI ; Wen TANG ; Zhanglin WANG ; Zhibin WANG ; Kang TONG ; Mingzhu LI ; Hairui HAN ; Duoduo LIN ; Shaodong ZHANG ; Huangwei LEI ; Yang WANG ; Candong LI
Journal of Beijing University of Traditional Chinese Medicine 2024;47(6):760-764
The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.
9.Investigation on Preventive Effect of Total Saponins of Notoginseng Radix et Rhizoma on Aspirin-induced Small Intestine Injury Based on Serum Metabolomics
Wenhui LIU ; Guodong HUA ; Baochen ZHU ; Ruoyu GAO ; Xin HUANG ; Meng WANG ; Zheng LIU ; Jiaojiao CHENG ; Zhibin SONG ; Jingui WANG ; Chunmiao XUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):196-203
ObjectiveMetabolomics was utilized to investigate the preventive effect of notoginseng total saponins(NTS) on aspirin(acetyl salicylic acid, ASA)-induced small bowel injury in rats. MethodFifty male SD rats were randomly divided into normal and model groups, NTS high-dose and low-dose groups(62.5, 31.25 mg·kg-1), and positive drug group(omeprazole 2.08 mg·kg-1+rebamipide 31.25 mg·kg-1), with 10 rats in each group. Except for the normal group, rats in other groups were given ASA enteric-coated pellets 10.41 mg·kg-1 daily to establish a small intestine injury model. On this basis, each medication group was gavaged daily with the corresponding dose of drug, and the normal group and the model group were gavaged with an equal amount of drinking water. Changes in body mass and fecal characteristics of rats were recorded and scored during the period. After 14 weeks of administration, small intestinal tissues of each group were taken for hematoxylin-eosin(HE) staining, scanning electron microscopy to observe the damage, and the apparent damage of small intestine was scored. Serum from rats in the normal group, the model group, and the NTS high-dose group was taken and analyzed for metabolomics by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS), and the data were processed by multivariate statistical analysis, the potential biomarkers were screened by variable importance in the projection(VIP) value≥1.0, fold change(FC)≥1.5 or ≤0.6 and t-test P<0.05, and pathway enrichment analysis of differential metabolites was performed in conjunction with Human Metabolome Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG). ResultAfter 14 weeks of administration, the average body mass gain of the model group was lower than that of the normal group, and the NTS high-dose group was close to that of the normal group. Compared with the normal group, the fecal character score of rats in the model group was significantly increased(P<0.05), and compared with the model group, the scores of the positive drug group and the NTS high-dose group were reduced, but the difference was not statistically significant. HE staining and scanning electron microscopy results showed that NTS could significantly improve ASA-induced small intestinal injury, compared with the normal group, the small bowel injury score of the model group was significantly increased(P<0.01), compared with the model group, the small bowel injury scores of the NTS low and high dose groups were significantly reduced(P<0.05, P<0.01). Serum metabolomics screened a total of 75 differential metabolites between the normal group and the model group, of which 55 were up-regulated and 20 were down-regulated, 76 differential metabolites between the model group and the NTS groups, of which 14 were up-regulated and 62 were down-regulated. NTS could modulate three differential metabolites(salicylic acid, 3-hydroxybenzoic acid and 4-hydroxybenzoic acid), which were involved in 3 metabolic pathways, namely, the bile secretion, the biosynthesis of folic acid, and the biosynthesis of phenylalanine, tyrosine and tryptophan. ConclusionNTS can prevent ASA-induced small bowel injury, and the underlying mechanism may be related to the regulation of bile secretion and amino acid metabolic pathways in rats.
10.Effect of Danhe Granules on Hypercholesterolemia Rats Based on Cholesterol Metabolism Pathway-related Proteins
Shiqiu TIAN ; Zeping ZUO ; Yingying TIAN ; Yilin LI ; Hailuan PEI ; Zhaozhou LIN ; Yingnan LYU ; Jianfang WANG ; Zhibin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):85-94
ObjectiveTo explore the therapeutic effect and mechanism of the Danhe granules on hypercholesterolemia rats by observing the changes in the efficacy indicators and the levels of proteins related to the cholesterol metabolism pathway in the rats under the intervention of Danhe granules. MethodSD rats were randomly assigned to either the blank group or the model group based on their body weight. The blank group had normal chow diets, while the model group was fed high-fat diets for seven weeks. One week after the establishment of the model, the content of the serum total cholesterol (TC) in the model rats was detected. According to the TC value, the model group was further randomly divided into a control group, pravastatin sodium tablet group(4.02 mg·kg-1), Xuezhikang capsule group(0.12 g·kg-1), high-dose, middle-dose, and low-dose groups of Danhe granules(4.536, 2.268, 1.134 g·kg-1). After grouping the model groups, each treatment group received continuous oral gavage for six weeks, with weekly measurements of body weight and food intake (the difference between feed intake and feed surplus). Six weeks later, the levels of serum TC, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. The liver pathology and lipid droplet distribution were evaluated by hematoxylin-eosin (HE) staining and oil red O staining, with scoring and calculation conducted. Rat liver tissue was collected, and western blot and immunohistochemistry (IHC) were used to detect the expression levels of cholesterol metabolism-related proteins namely phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK), AMPK, 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), low-density lipoprotein receptor (LDLR), cholesterol 7α-hydroxylase (CYP7A1), Acyl-coenzyme A: cholesterol acyltransferase 2 (ACAT2), and apolipoprotein B (ApoB) in hypercholesterolemia rats. ResultCompared with the blank group, the model group showed a significantly higher level of serum TC (P<0.01). The TG level had no significant change, and the HDL-C level was significantly decreased (P<0.05). The liver index, steatosis score, total score of pathological state, and the positive area ratio of oil red O staining were significantly increased (P<0.01), and the protein expression levels of p-AMPK, p-AMPK/AMPK, LDLR, and CYP7A1 were significantly decreased (P<0.05, P<0.01), while the protein expression levels of AMPK, HMGCR, and ACAT2 were significantly increased (P<0.05, P<0.01). Compared with the model group, the TC level in each dose group of Danhe granules was significantly decreased (P<0.05), and the positive area ratio of oil red O staining in the pravastatin sodium tablet group and medium-dose group of Danhe granules was significantly decreased (P<0.05). In each administration group, the protein expression levels of p-AMPK and p-AMPK/AMPK were significantly increased (P<0.05, P<0.01), and the levels of HMGCR and ACAT2 were significantly decreased (P<0.01). The ApoB level showed a downward trend. The CYP7A1 level in the pravastatin sodium tablet group and each dose group of Danhe granules was significantly increased (P<0.05, P<0.01), and the LDLR level in the pravastatin sodium tablet group, Xuezhikang capsule group, and high-dose and medium-dose groups of Danhe granules was significantly increased (P<0.05, P<0.01). ConclusionDanhe granules can reduce serum TC levels and improve hepatic steatosis. It may activate AMPK, down-regulate the expression of HMGCR, and inhibit cholesterol synthesis. It can also up-regulate the expression of LDLR and CYP7A1, promote cholesterol uptake and excretion, down-regulate the expression of ACAT2 and ApoB, reduce cholesterol absorption and assembly of LDL and other lipoproteins, and thus play a role in the treatment of hypercholesterolemia.


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