1.The distribution pattern of traditional Chinese medicine syndromes and influencing factors for primary liver cancer: An analysis of 415 cases
Zhiyao SHI ; Xiaofei FAN ; Yu GAO ; Shaojian REN ; Shiyu WU ; Xixing WANG
Journal of Clinical Hepatology 2025;41(1):84-91
ObjectiveTo investigate the influencing factors for traditional Chinese medicine (TCM) syndromes of primary liver cancer, and to provide a theoretical basis for the TCM syndrome differentiation and standardized treatment of liver cancer. MethodsTCM syndrome differentiation was performed for 415 patients who were admitted to Shanxi Institute of Traditional Chinese Medicine and were diagnosed with primary liver cancer based on pathological or clinical examinations from January 2019 to December 2023. The chi-square test was used for comparison of categorical data between groups, and the unordered polytomous logistic regression model was used to investigate the influencing factors for TCM syndromes of liver cancer. ResultsThe common initial symptoms of the 415 patients with primary liver cancer included pain in the liver area (31.81%), abdominal distension (25.30%), abdominal pain (15.18%), and weakness (13.98%), and the main clinical symptoms included poor appetite (70.84%), fatigue (69.16%), pain in the liver area (67.47%), poor sleep (59.04%), abdominal distension (53.01%), and constipation (52.53%). There were significant differences in TCM syndromes between patients with different sexes, courses of the disease, clinical stages, Child-Pugh classes, presence or absence of intrahepatic and extrahepatic metastasis, and presence or absence of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (all P<0.05). The logistic regression analysis showed that male sex was a risk factor for damp-heat accumulation (odds ratio [OR]=2.036, P=0.048) and the syndrome of spleen-kidney Yang deficiency (OR=5.240, P<0.001); a course of disease of<1 year was a risk factor for damp-heat accumulation (OR=2.837, P=0.004) and syndrome of Qi stagnation and blood stasis (OR=2.317, P=0.021), but it was a protective factor against syndrome of spleen-kidney Yang deficiency (OR=0.385, P=0.005); Child-Pugh class A/B was a protective factor against liver-kidney Yin deficiency (OR=0.079, P<0.001); intrahepatic metastasis was a risk factor for liver-kidney Yin deficiency (OR=5.117, P=0.003) and syndrome of spleen-kidney Yang deficiency (OR=3.303, P=0.010); TACE was a protective factor against liver-kidney Yin deficiency (OR=0.171, P<0.001) and syndrome of spleen-kidney Yang deficiency (OR=0.138, P<0.001); radiofrequency ablation was a risk factor for damp-heat accumulation (OR=4.408, P<0.001) and liver-kidney Yin deficiency (OR=32.036, P<0.001). ConclusionSex, course of disease, Child-Pugh class, intrahepatic metastasis, TACE, and radiofrequency ablation are the main influencing factors for TCM syndromes of liver cancer.
2.Effect of auricular therapy on sleep improvement and the GABAergic system pathway in an insomnia rat model
Hao CHEN ; Xifen ZHANG ; Xuesong WANG ; Yuanbo GAO ; Xuxin LI ; Xihui ZHENG ; Yu WANG ; Xiaojun ZHENG ; Haiping LI ; Yanfen SHE
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):138-148
Objective:
To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism.
Methods:
According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats.
Results:
Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05).
Conclusion
Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.
3.Role of autophagy in treatment of paracetamol-induced liver injury
Guojing XING ; Lifei WANG ; Longlong LUO ; Xiaofeng ZHENG ; Chun GAO ; Xiaohui YU ; Jiucong ZHANG
Journal of Clinical Hepatology 2025;41(2):389-394
N-acetyl-p-aminophenol (APAP) is an antipyretic analgesic commonly used in clinical practice, and APAP overdose can cause severe liver injury and even death. In recent years, the incidence rate of APAP-induced liver injury (AILI) tends to increase, and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI, involving the mechanisms such as APAP protein conjugates, oxidative stress, JNK activation, mitochondrial dysfunction, inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI, in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.
4.Effect of Huanglian Jiedutang in Regulating Ferroptosis in Mice with Atherosclerosis Based on Nrf2/GPX4 Signaling Pathway
Zhaohui GONG ; Li GAO ; Huiqi ZHAI ; Jinzi YU ; Qingmin CHU ; Chuanjin LUO ; Lijin QING ; Wei WU ; Rong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):22-28
ObjectiveTo study the mechanism of Huanglian Jiedutang (HLJDT) in treating mice with atherosclerosis (AS) by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group, and 50 ApoE-/- mice were randomly divided into five groups: model group, low-dose group of HLJDT, medium-dose group of HLJDT, high-dose group of HLJDT, and atorvastatin (ATV) group. ApoE-/- mice were fed a high-fat diet for eight weeks to establish the AS model, and at the 9th week, they were given normal saline, low, medium, and high doses of HLJDT (3.9, 7.8, 15.6 g·kg-1·d-1), and atorvastatin calcium tablets (0.01 g·kg-1·d-1), respectively, for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in blood fat were measured by the automatic biochemical analyzer, and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase (SOD) in serum was detected by enzyme-linked immunosorbent assay (ELISA). The content of reduced glutathione (GSH) in serum was detected by the microplate method, and that of malondialdehyde (MDA) in serum was detected by the TBA method. The protein expression of nuclear factor E2-associated factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway was detected by Western blot. ResultsCompared with those of the normal group, the contents of TC, LDL-C, TG, HDL-C, and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased (P<0.01), while the expression levels of SOD and GSH in serum, as well as Nrf2, solute carrier family 7 member 11 (SLC7A11), and GPX4 in aorta were significantly decreased (P<0.01). Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta, volume atrophy, mitochondrial crista reduction, or a loose and disorganized form. Compared with those in the model group, the aortic vascular plaque deposition was significantly decreased in the low-dose, medium-dose, and high-dose groups of HLJDT and ATV group, and the contents of serum TC, LDL-C, TG, and MDA in serum were significantly decreased (P<0.05, P<0.01). The contents of serum SOD and GSH and the expression levels of Nrf2, SLC7A11, and GPX4 in the aorta were increased (P<0.05, P<0.01), and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased, and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition, decrease blood lipid and MDA expression, increase SOD and GSH expression, and ameliorate the pathological changes of ferroptosis, the mechanism of which is related to the Nrf2/GPX4 signaling pathway.
5.Mechanism of Buyang Huanwutang in Inhibiting Ferroptosis and Enhancing Neurological Function Recovery After Spinal Cord Injury via GPX4-ACSL4 Axis
Luchun XU ; Guozheng JIANG ; Yukun MA ; Jiawei SONG ; Yushan GAO ; Guanlong WANG ; Jiaojiao FAN ; Yongdong YANG ; Xing YU ; Xiangsheng TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):20-30
ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 (GPX4)-acyl-CoA synthetase long-chain family member 4 (ACSL4) axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury (SCI). MethodsNinety rats were randomly divided into five groups: sham operation group, model group, low-dose Buyang Huanwutang group (12.5 g·kg-1), high-dose Buyang Huanwutang group (25 g·kg-1), and Buyang Huanwutang + inhibitor group (25 g·kg-1 + 5 g·kg-1 RSL3). The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan (BBB) scale. Hematoxylin-eosin (HE), Nissl, and Luxol fast blue (LFB) staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein (MBP), GPX4, and ACSL4. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group, the model group exhibited significantly reduced BBB scores (P<0.01), severe pathological damage in spinal cord tissue, and marked mitochondrial ultrastructural disruption. In addition, the model group showed a decrease in the number of NeuN-positive cells (P<0.01), reduced fluorescence intensity of MBP and GPX4 (P<0.01), lower levels of GSH and SOD (P<0.01), and downregulated mRNA expression of GPX4 (P<0.01). Moreover, compared to the sham operation group, the model group had elevated levels of ROS, MDA, and tissue iron content (P<0.01), along with increased fluorescence intensity and mRNA expression of ACSL4 (P<0.01). Compared with the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group showed significantly improved BBB scores (P<0.05, P<0.01) and exhibited less severe spinal cord tissue damage, reduced edema and inflammatory cell infiltration, increased neuronal survival, and more intact myelin structures. Additionally, mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP (P<0.05, P<0.01). Furthermore, Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 (P<0.01) and decreased the fluorescence intensity and mRNA expression of ACSL4 (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. Finally, the Buyang Huanwutang group significantly decreased ROS, MDA, and tissue iron content (P<0.01) and significantly increased GSH and SOD levels (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis, reduces secondary neuronal and myelin injury and oxidative stress, and ultimately promotes the recovery of neurological function.
6.Mechanism of inhibitory effect of total flavonoids from Taraxacum mongolicum on obesity in mice by regulating intestinal flora
Yixue GAO ; Lin GUO ; Linyan LANG ; Jing WU ; Haoyang WANG ; Jing YANG ; Mingsan MIAO ; Zhanzhan LI
China Pharmacy 2025;36(3):293-299
OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group, model group and T. mongolicum total flavonoid group, with 8 mice in each group. Except for the blank group, the other 2 groups were given a high-fat diet, while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/(kg·d)] intragastrically, once a day, for 8 consecutive weeks. During the experiment, the food intake of each group of mice was recorded. After the last medication, the body mass, fat weight, blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing; the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group, the body weight of mice in T. mongolicum total flavonoids group was decreased significantly (P<0.05); the levels of total lipid cholesterol, triglycerides, and LDL cholesterol were all decreased significantly (P<0.01), and the level of HDL cholesterol was increased significantly (P<0.01); the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced (P<0.05); significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved; mRNA expressions of COX7A1 and COX8B were significantly upregulated (P<0.05). The results of bacterial colony detection showed that compared with the model group, there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group, and the Sobs index characterization and β diversity were increased significantly (P<0.05). Relative abundances of Blautia, norank_f_Ruminococcaceae, Bilophila, Alistipes, classified_f_Ruminococcaceae, Parabacteroides, norank_f_Desulfovibrionaceae, Anaerotruncus were significantly up-regulated(P<0.05), while those of Faecalibaculum, Erysipelatoclostridium, GCA-900066575, Tuzzerella, Lactobacillus, norank_f_norank_o_RF39, achnospiraceae_FCS020_group were significantly down-regulated (P<0.05). CONCLUSIONS T. mongolicum total flavonoids can reduce body mass, fat weight and blood lipid levels, and repair the pathological damage to liver and epididymal fat in obese mice, which is related to improving intestinal flora disorders caused by high-fat diet.
7.Prevalence and influencing factors of school bullying experienced by primary and middle school students
ZHU Yunjiao ; GU Fang ; MENG Jia ; LI Juanjuan ; SHEN Yu ; GAO Lei
Journal of Preventive Medicine 2025;37(1):1-6
Objective:
To investigate the situation and influencing factors of school bullying experienced by primary and middle school students, so as to provide the basis for formulating school bullying intervention measures and promoting students' physical and mental health development.
Methods:
All the counties (cities, districts) in Zhejiang Province were stratified to urban and suburban areas, primary, junior high and senior high school students were selected using a stratified cluster sampling method. Basic information, lifestyle and school bullying were collected through questionnaire surveys. Factors affecting school bullying experienced by primary and middle school students were analyzed using a multivariable logistic regression model.
Results:
Totally 137 846 valid questionnaires were recovered, with an effective recovery rate of 97.17%. There were 72 526 males (52.61%) and 65 320 females (47.39%). There were 47 561 primary school students (34.50%), 47 701 junior high school students (34.61%) and 42 584 senior high school students (30.89%). A total of 3 987 students suffered from school bullying, accounting for 2.89%. The proportions of being maliciously teased, being intentionally excluded from group activities/isolated, being teased about physical defects or appearance, being hit/kicked/pushed/shoved/locked in a room, being threatened, and being extorted for money were 2.04%, 1.18%, 1.11%, 0.86%, 0.84% and 0.83%, respectively. Multivariable logistic regression analysis showed that the students who were males (OR=1.122, 95%CI: 1.048-1.202), lived in suburban areas (OR=1.322, 95%CI: 1.233-1.418), lived in areas with medium (OR=1.086, 95%CI: 1.006-1.173) or underdeveloped (OR=1.298, 95%CI: 1.191-1.415) economic level, had higher academic levels (junior high school, OR=1.380, 95%CI: 1.270-1.499; senior high school, OR=1.210, 95%CI: 1.083-1.351), lived on campus (OR=1.489, 95%CI: 1.372-1.616), engaged in fights (OR=6.029, 95%CI: 5.585-6.509), attempted to smoke (OR=1.320, 95%CI: 1.128-1.545), drank (OR=1.735, 95%CI: 1.575-1.912), were scolded and beaten by parents (OR=1.972, 95%CI: 1.822-2.135) and were obese (OR=1.240, 95%CI: 1.132-1.360) were more likely to experience school bullying.
Conclusion
The harm of school bullying to the physical and mental health of primary and middle school students should be taken seriously, and active policy measures should be adopted to strengthen intervention.
8.Availability and use of child safety seats among children aged 0-3 years
CHEN Bo ; WANG Xihui ; QIU Fengqian ; YU Yan ; GAO Shuna ; HE Lihua ; LI Weiyi ; JI Yunfang ; CHEN Weihua
Journal of Preventive Medicine 2025;37(1):21-25
Objective:
To investigate the availability and use of child safety seats among children aged 0-3 years, so as to provide the basis for improving riding safety for children.
Methods:
Parents of children aged 0-3 years in Huangpu District, Shanghai Municipality, were recruited using the stratified multistage random sampling method from May to July 2024. Demographic information, family travel patterns, the use of child safety seat and related health beliefs were collected using questionnaire surveys. Factors affecting the use of child safety seats were identified using a multivariable logistic regression model.
Results:
Totally 514 valid questionnaires were recovered, with an effective rate of 96.98%. The respondents included 122 fathers (23.74%) and 392 mothers (76.26%), with a median age of 34.00 (interquartile range, 5.00) years. There were 446 families equipping with child safety seats, accounting for 86.77%; and 169 families using child safety seats, accounting for 32.88%. Multivariable logistic regression analysis showed that the parents who had children aged >1-2 years (OR=0.597, 95%CI: 0.366-0.973), travelled 2-4 times per month (OR=0.359, 95%CI: 0.213-0.607) or once per month or less (OR=0.384, 95%CI: 0.202-0.729), and scored high in perceived barrier (OR=0.634, 95%CI: 0.486-0.827) were less likely to use child safety seats; the parents who had children with local household registration (OR=2.506, 95%CI: 1.356-4.633), travelled 5-<10 km (OR=1.887, 95%CI: 1.148-3.101) or ≥10 km (OR=2.319, 95%CI: 1.355-3.967), always wore seat belts (OR=2.342, 95%CI: 1.212-4.524), scored high in perceived susceptibility (OR=1.392, 95%CI: 1.091-1.778) and self-efficacy (OR=1.413, 95%CI: 1.156-1.727) were more likely to use child safety seats.
Conclusions
Equipping family cars with child safety seats and using them can prevent and reduce traffic injuries among children aged 0-3 years. It is recommended to strengthen publicity to promote the use of child safety seats.
9.Analysis on Acupuncture in the Treatment of Post-stroke Dysphagia Based on the Theory of "Latent Pathogen in Cerebral Collaterals"
Hongtao LI ; Yaqi HUANG ; Lulu YAO ; Bing GAO ; Yu YE ; Nenggui XU ; Lin WANG
Journal of Traditional Chinese Medicine 2025;66(9):901-905
Dysphagia is a common complication of stroke. Combining the principles of traditional Chinese medicine with modern research findings, it is proposed that "latent pathogen in the cerebral collaterals" constitutes the core pathogenesis of post-stroke dysphagia (PSD). In clinical practice, treatment is tailored according to the location of PSD. During the oral stage, when the pathogen invades the face and mouth, resulting in excessive salivation, acupoints are primarily selected from the foot shaoyin (少阴) kidney channel, in combination with ren mai (任脉) , du mai (督脉), chong mai (冲脉) and the spleen channel, to replenish essence and fill the marrow, dispel dampness and unblock the channels. In the pharyngeal stage, as the pathogen obstructs the throat, disrupting normal swallowing, the therapy emphasizes dredging the shaoyang (少阳) channel and warming and tonifying the jueyin (厥阴) channel, by taking acupoints mainly from the hand and foot shaoyang channels, along with the jueyin channels, so as to soothe the liver and promote bile secretion, regulate and harmonize qi and blood. During the esophageal stage, where the pathogen damages the esophagus, impeding food passage, the treatment emphasizes activating the yangming (阳明) channels and regulating taiyin (太阴) channels; acupoints are mainly selected from the foot yangming stomach channel, along with the taiyin channels, aiming to warm yang, unblock the channels and dispel stasis.
10.The mechanism of Laggerae Herba in improving chronic heart failure by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signaling pathway
Jinling XIAO ; Kai HUANG ; Xiaoqi WEI ; Xinyi FAN ; Wangjing CHAI ; Jing HAN ; Kuo GAO ; Xue YU ; Fanghe LI ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):343-353
Objective:
To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice.
Methods:
Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue.
Results:
Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group.
Conclusion
Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.


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