1.Mechanism of Danshenol A in Alleviating Myocardial Ischemia-reperfusion Injury-induced Ferroptosis of Cardiomyocytes
Lei ZHANG ; Jiangang LIU ; Peili WANG ; Tao GENG ; Die LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):135-144
ObjectiveTo investigate the mechanism of danshenol A (DA) pretreatment in alleviating myocardial ischemia-reperfusion injury (MIRI) by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats, and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank, model (OGD/R), DA, ferroptosis inducer (erastin), and ferroptosis inhibitor (Fer-1) groups. Cell viability was assessed by the methyl thiazolyl tetrazolium (MTT) assay. Biochemical assays were performed to measure the superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) levels. Dihydroethidium (DHE) fluorescence assay was adopted to quantify the reactive oxygen species (ROS) level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels, respectively, of prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-coA synthetase long-chain family 4 (ACSL4). Sixty SPF-grade healthy male SD rats were randomly assigned to control, model (MIRI), DA, erastin, and Fer-1 groups. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum levels of cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and creatine kinase (CK). Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL). The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment: compared with the blank group, the OGD/R model group showed reduced cell viability, elevated levels of ROS, MDA, and Fe2+, up-regulated mRNA and protein levels of ACSL4, lowered levels of SOD and GSH, and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05,P<0.01). The DA and Fer-1 groups exhibited consistent trends: cell viability, SOD and GSH levels, and the mRNA and protein levels of PTGS2, GPX4, and FTH1 were significantly restored, while the ROS, MDA, and Fe2+ levels, and the mRNA and protein levels of ACSL4 were reduced (P<0.05,P<0.01). In vivo experiment: Compared with the control group, the MIRI model group showed elevated serum levels of cTnI, LDH, and CK, increased cardiomyocyte apoptosis rate, risen levels of ROS, MDA, and Fe2+, and up-regulated mRNA and protein levels of ACSL4. However, both DA and Fer-1 groups exhibited reductions in the indicators above (P<0.05). Compared with the control group, the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05). In contrast, both DA and Fer-1 upregulated these indicators (P<0.05), effectively reversing the trends in the model group. In addition, the MIRI model group showed swelling of cardiomyocytes, disarrangement of cardiac muscle fibers, and massive inflammatory cell infiltration, which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation, demonstrating therapeutic potential in acute myocardial infarction.
2.Mechanism of Danshenol A in Alleviating Myocardial Ischemia-reperfusion Injury-induced Ferroptosis of Cardiomyocytes
Lei ZHANG ; Jiangang LIU ; Peili WANG ; Tao GENG ; Die LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):135-144
ObjectiveTo investigate the mechanism of danshenol A (DA) pretreatment in alleviating myocardial ischemia-reperfusion injury (MIRI) by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats, and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank, model (OGD/R), DA, ferroptosis inducer (erastin), and ferroptosis inhibitor (Fer-1) groups. Cell viability was assessed by the methyl thiazolyl tetrazolium (MTT) assay. Biochemical assays were performed to measure the superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) levels. Dihydroethidium (DHE) fluorescence assay was adopted to quantify the reactive oxygen species (ROS) level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels, respectively, of prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-coA synthetase long-chain family 4 (ACSL4). Sixty SPF-grade healthy male SD rats were randomly assigned to control, model (MIRI), DA, erastin, and Fer-1 groups. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum levels of cardiac troponin I (cTnI), lactate dehydrogenase (LDH), and creatine kinase (CK). Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL). The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment: compared with the blank group, the OGD/R model group showed reduced cell viability, elevated levels of ROS, MDA, and Fe2+, up-regulated mRNA and protein levels of ACSL4, lowered levels of SOD and GSH, and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05,P<0.01). The DA and Fer-1 groups exhibited consistent trends: cell viability, SOD and GSH levels, and the mRNA and protein levels of PTGS2, GPX4, and FTH1 were significantly restored, while the ROS, MDA, and Fe2+ levels, and the mRNA and protein levels of ACSL4 were reduced (P<0.05,P<0.01). In vivo experiment: Compared with the control group, the MIRI model group showed elevated serum levels of cTnI, LDH, and CK, increased cardiomyocyte apoptosis rate, risen levels of ROS, MDA, and Fe2+, and up-regulated mRNA and protein levels of ACSL4. However, both DA and Fer-1 groups exhibited reductions in the indicators above (P<0.05). Compared with the control group, the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2, GPX4, and FTH1 (P<0.05). In contrast, both DA and Fer-1 upregulated these indicators (P<0.05), effectively reversing the trends in the model group. In addition, the MIRI model group showed swelling of cardiomyocytes, disarrangement of cardiac muscle fibers, and massive inflammatory cell infiltration, which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation, demonstrating therapeutic potential in acute myocardial infarction.
3.Research progress on the prevention and treatment of myocardial infarction by traditional Chinese medicine through regulating NF-κB signaling pathway
Lirong ZHENG ; Peili YANG ; Guiwei LI ; Junchi GUO ; Yingqiang ZHAO
China Pharmacy 2025;36(14):1807-1812
Myocardial infarction (MI) refers to an acute clinical syndrome of myocardial necrosis due to persistent ischemia and hypoxia, resulting from the sharp reduction or interruption of coronary blood flow. Nuclear factor κB (NF-κB) is the key factor in inducing inflammatory response, and it is involved in the production of pro-inflammatory factors and myocardial cell apoptosis. This article systematically describes the molecular regulation mechanism of the NF-κB signaling pathway in MI, and reviews the related research on the prevention and treatment of MI through the regulation of this signaling pathway by active ingredients and compound formulas from traditional Chinese medicine (TCM). It has been found that active ingredients from TCM, such as ginsenoside Rg3, baicalein, curcumin, tanshinone ⅡA, gambogic acid, as well as compound formulas, including Qili qiangxin capsules, Yiqi huoxue decoction, Lingbao huxin dan, Danhong injection, Baoyuan decoction combined with Taohong siwu decoction, can improve myocardial fibrosis, alleviate inflammatory responses, and inhibit cardiomyocyte apoptosis by suppressing the NF-κB signaling pathway. Thereby, they achieve the goal of preventing and treating MI.
4.Regulation of Oxidative Stress by Traditional Chinese Medicine in Prevention and Treatment of Myocardial Ischemia-reperfusion Injury: A Review
Haosen ZHAO ; Weijie REN ; Jiahao LI ; Peili WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):268-276
Myocardial ischemia-reperfusion injury (MIRI) is a major complication following coronary revascularization. Studies indicate that its pathophysiological mechanisms of MIRI are closely associated with oxidative stress, iron overload, inflammatory responses, and lipid peroxidation. Oxidative stress refers to an imbalance in redox homeostasis under pathological conditions, characterized by the abnormal accumulation of reactive oxygen species (ROS), which disrupts the dynamic balance between pro-oxidant systems and antioxidant defense networks. In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in the prevention and treatment of MIRI due to its multi-target and multi-pathway antioxidant properties. Research reveals that TCM primarily exerts protective effects against oxidative stress-induced MIRI by regulating signaling pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2), adenosine monophosphate-activated protein kinase (AMPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), nuclear factor kappa-B (NF-κB), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and protein kinase C beta Ⅱ/nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species (PKCβⅡ/NOX2/ROS). This article reviews recent literature on TCM monomers, compound formulas, and their active components, which alleviate oxidative stress to prevent and treat MIRI by modulating the aforementioned signaling pathways. It summarizes a concise overview of the molecular mechanisms by which oxidative stress-related signaling pathways lead to MIRI, discusses how TCM regulates these pathways to reduce oxidative stress-induced MIRI, and explores clinical application prospects and research challenges, aiming to provide a theoretical reference for the research and clinical management of MIRI.
5.Application of discharge preparation services in patients undergoing uniportal video-assisted thoracoscopic surgery for lung cancer
Qianqian SONG ; Aihong PAN ; Qing ZHANG ; Peili XU ; Shanshan LUO
Chinese Journal of Modern Nursing 2024;30(31):4270-4275
Objective:To explore the effect of discharge preparation services in patients undergoing uniportal video-assisted thoracoscopic surgery for lung cancer.Methods:A total of 192 lung cancer patients who underwent uniportal video-assisted thoracoscopic surgery between April 2021 and May 2023 were selected using a convenience sampling method. The 97 patients admitted from April 2021 to April 2022 were designated as the control group and received routine care, while the 95 patients admitted from May 2022 to May 2023 were designated as the observation group and received discharge preparation services. Postoperative recovery indicators (e.g., time to first meal, time to first ambulation), the Readiness for Hospital Discharge Scale (RHDS), the Chinese version of the Functional Assessment of Cancer Therapy-Lung (FACT-L), and the nursing service satisfaction questionnaire were used to evaluate the intervention's effects.Results:The observation group had significantly shorter times to first meal, first ambulation, and drain removal, as well as lower complication rates compared to the control group, with statistically significant differences ( P<0.05). After the intervention, the RHDS, FACT-L, and nursing service satisfaction questionnaire scores were significantly higher in the observation group compared to the control group, with statistically significant differences ( P<0.05) . Conclusions:The application of discharge preparation services improves postoperative recovery, discharge readiness, quality of life, and satisfaction with nursing services in patients undergoing lung cancer surgery.
6.Method and improvement of implantable osmotic pump for intraventricular drug administration in rats
Heyong SUN ; Gangli ZHANG ; Jiliang WU ; Peili CAO ; Shuo LI ; Haoqin SUN
Chinese Journal of Comparative Medicine 2024;34(7):89-94
Objective To introduce and enhance an experimental technique for intraventricular drug delivery via an implantable osmotic pump.Methods Eight-week-old male SD rats were selected and the requisite equipment and reagents were prepared.The osmotic pump was assembled and brought to operational status before conducting the implantation surgery.Following anesthesia,the rats underwent skin preparation and the upper surface of the skull was surgically exposed.A point directly above the ventricle was located using a brain stereotaxic apparatus,and a small hole was drilled at that location with a high-speed cranial drill.The pump body was then implanted subcutaneously in the neck and the needle was inserted into the drilled hole,and secured with dental cement.Once solidified,the needle base was removed,the subcutaneous soft tissue and scalp were sutured in layers,and the animal was returned to its cage for rearing in isolation.Results The osmotic pump was successfully implanted subcutaneously in the rat's neck,the needle was securely fixed to the skull,and the catheter interface remained intact.The rats were sacrificed and the brain tissue was removed.Examination of the extracted brain tissue revealed no significant hematoma around the puncture site or needle tract,and the presence of blue dye in the ventricular and adjacent tissues indicated successful drug delivery to the ventricle.Conclusions The introduction of a brain stereotaxic apparatus to aid localization,coupled with enhancements to the operational procedure,may improve the accuracy and safety of the implantation process resulting in a high success rate for intraventricular drug administration.
7.Evidence summary of nutritional management of food for special medical purpose in postoperative adjuvant chemotherapy patients with cancer
Chaoyue GAO ; Min LI ; Yinzhu ZHANG ; Peili ZHANG ; Xiaoya HOU ; Yixia CHENG
Chinese Journal of Nursing 2024;59(8):934-941
Objective To summarize the best evidence of nutritional support therapy with food for special medi-cal purpose for patients undergoing adjuvant chemotherapy after oncology surgery,and to provide a reference basis for standardizing the application of food for special medical purpose and guiding clinical nutritional therapy practice for oncology patients.Methods Computer search was conducted on UpToDate,Guidelines International Network(GIN),National Guideline Clearinghouse,National Comprehensive Cancer Network,National Institute for Health and Clinical Excellence,Oncology Nursing Society,American Society for Parenteral Enteral Nutrition,European Society for Clinical Nutrition and Metabolism,Chinese Society for Parenteral and Enteral Nutrition,Joanna Briggs Institute Evidence-Based Health Care Centre database,Cochrane Library,PubMed,CINAHL,Scopus,Web of Science,Em-base,CBM,Wanfang,and China Knowledge Network on the nutritional support treatment of food for special medical purpose for postoperative adjuvant chemotherapy patients.The retrieval period was from January 2012 to August 2022.Quality evaluation of the literature was completed independently by 2 evidence-based trained researchers and combined with expert advice to extract and summarise evidence for the literature that met quality standards.Results A total of 14 articles were included,including 4 guidelines,1 clinical decision,2 systematic re views,4 expert consen-suses,and 3 randomized controlled trials.The 14 pieces of best evidence were compiled,covering 6 aspects of nu-tritional screening and assessment,nutritional education,recommended dose,formulation selection,nutritional treat-ment,and management of adverse effects.Conclusion This study summarises the best evidence on the nutritional management of food for special medical purpose in postoperative adjuvant chemotherapy patients with cancer,which is scientific and systematic.When administering nutritional therapy to patients,healthcare professionals should fully assess the nutritional status of patients,make clear and prudent choices on the dosage and type of food for special medical puipose to be used by patients,and guide patients to improve their nutritional status safely and effectively to improve their quality of life.To improve the quality of life.
8.Analysis on the value of 2DE combined with CDFI in diagnosing HCM
Yu ZHANG ; Peili AN ; Ning WANG ; Shujuan ZHONG
China Medical Equipment 2024;21(5):83-87
Objective:To observe the value of two-dimensional echocardiography(2DE)combined with color Doppler flow imaging(CDFI)in the diagnosis for hypertrophic cardiomyopathy(HCM).Methods:A total of 480 HCM patients who admitted to Northwest Women's and Children's Hospital from January 2019 to January 2021 were selected as case group,and 200 healthy individuals who underwent health physical examination were included into health control group.All receivers underwent 2DE and CDFI examinations,and the 2DE and CDFI detection indicators of two groups were calculated by statistical method and were compared.The diagnostic efficacies of single 2DE,single CDFI and the combination of them were analyzed.Results:The thickness of left ventricular posterior wall(LVPW),interventricular septum thickness(IVST)and left atrial diameter(LAD)of the case group were significantly higher than those of the control group,and the differences were statistically significant(t=5.896,14.861,8.974,P<0.05),respectively.The E peak/A peak(E/A)of anterior flow of mitral valve and early diastolic velocity of mitral valve(Em)of the case group were respectively lower than those of the health control group,while the early diastolic blood flow velocity of mitral valve opening(E)/Em(E/Em)of the case group was higher than that of the health control group,with statistically significant differences(t=6.782,5.189,10.738,P<0.05).The optimal critical points(detection sensitivity)of the receiver operating characteristic(ROC)curves of single 2DE,single CDFI and combination of them in diagnosing HCM were respectively 67.83%,65.38%and 82.38%.The detection specificities of them were respectively 65.48%,64.58%and 80.66%.The area under curve(AUC)values of ROC curves of them were respectively 0.6835,0.6949 and 0.8136,and the accuracies of them were respectively 68.35%,69.49%and 81.36%,and the 95%confidence intervals of them were respectively 0.608-0.803,0.606-0.823 and 0.835-0.943.The sensitivity,specificity and accuracy of the combination of 2DE and CDFI were respectively higher than those of single 2DE and CDFI.Conclusion:Both 2DE and CDFI have a certain value in diagnosing HCM,but their combination can further improve the diagnostic efficacy for HCM.
9.Zoledronic acid affects osteogenic differentiation and bone formation by regulating the expression of SIRT3/P53
Jie HAN ; Letian QIAO ; Xiaoyi WANG ; Huihui CHEN ; Naying CHU ; Peili CHEN
Chinese Journal of Endocrine Surgery 2024;18(1):130-137
Objective:To explore the mechanism of zoledronic acid (ZOL) affects osteogenic differentiation and bone formation through the regulation of sirtuin 3 (SIRT3) / P53 expression.Methods:Bone marrow mesenchymal stem cells (BMSCs) were induced to differentiate into osteogenic cells, the expression of SIRT3 in the cells was detected, and the targeting regulation relationship between SIRT3 and P53 was analyzed. The intracellular expressions of SIRT3 and P53 were intervened and ZOL was used to treat the cells. MTT method, Western blot method and kit were used to detect cell viability, osteogenesis-related genes Osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2) expression, alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining, respectively. Ovariectomy (OVX) was used to construct a rat model and explore the effect of ZOL on the progression of osteoporosis (OP) in vivo.Results:ZOL promoted osteogenic differentiation of BMSCs. The expression of SIRT3 was down-regulated in the serum of OP patients (0.78±0.23) compared with that of healthy subjects (1.00±0.26 vs. 0.78±0.23. t=3.85, P<0.001). During the osteogenic differentiation of BMSCs, the expression level of SIRT3 gradually increased with the prolonged induction of osteogenesis. Compared with the p53 protein expression and BMSCs activity in the control group, SIRT3 knockout could increase the expression level of p53 protein (0.59±0.05 vs. 1.01±0.11. t=6.02, P=0.004) but inhibited the activity of BMSCs (100.00±8.41 vs. 51.26±5.59. t=8.36, P=0.001). After ZOL treatment, the inhibitory effect of SIRT3 on cell viability (49.61±5.11 vs. 87.61±7.31. t=7.38, P=0.002) and osteogenesis was relieved, and the level of P53 was inhibited (1.10±0.10 vs. 0.69±0.04. t=6.59, P=0.003). P53 overexpression partially offseted the effects of ZOL on cell viability (84.61±6.52 vs. 66.54±5.47. t=3.68, P=0.021) and osteogenesis. Compared with the sham surgery group, the OVX group showed inhibition of osteogenesis in rats, and ZOL treatment significantly improved osteogenic inhibition. ZOL treatment increased the expression level of SIRT3 protein in bone tissue of OVX rats, but inhibited the expression level of P53. Conclusion:ZOL promoted osteogenic differentiation and bone formation of BMSCs by promoting the ubiquitination and degradation of P53 by SIRT3.
10.Effects of simethicone on gastrointestinal hormones,intestinal floras and inflammatory process mediated by NLRP3 inflammasome in patients with irritable bowel syndrome
Xin LING ; Jiaping QIAN ; Dong-Tao SHI ; Jun YANG ; Peili FEI
The Journal of Practical Medicine 2024;40(2):237-241
Objective To explore the effects of simethicone on gastrointestinal hormones,intestinal floras and inflammatory process mediated by NOD-like receptor protein 3(NLRP3)inflammasome in patients with irritable bowel syndrome(IBS).Methods A total of 120 patients with IBS admitted to the hospital were prospectively enrolled as the research objects between January 1,2021 and December 31,2022,and they were randomly divided into control group(60 cases)and treatment group(60 cases).The control group was treated with compound eosinophil-Lactobacillus,while treatment group was additionally treated with simethicone.The curative effect after treatment,scores of gastrointestinal symptom rating scale(GSRS),levels of somatostatin(SS),vasoactive intestinal peptide(VIP),NLRP3 inflammasome,interleukin-8(IL-8)and interleukin-1β(IL-1β),counts of intestinal floras before and after treatment,and safety during treatment were compared between the two groups.Results After treatment,total response rate of treatment group was higher than that of control group(91.67% vs.76.67% ,P<0.05).After treatment,GSRS scores in both groups were decreased,which were lower in treatment group than control group(P<0.05).After treatment,levels of SS and VIP in both groups were decreased,which were lower in treatment group than control group(P<0.05).After treatment,counts of eosinophil-Lactobacillus and Bifidobacteria were increased in both groups,the difference was statistically significant(P<0.05),but there was no significant difference in counts of intestinal floras between the two groups(P>0.05).After treatment,levels of NLRP3 inflammasome,IL-8 and IL-1β were decreased in both groups,the difference was statistically significant(P<0.05),but there was no significant difference between the two groups(P>0.05).During treatment,there was no significant difference in side effects between the two groups(P>0.05).Conclusion Simethicone can significantly improve response rate of treatment,improve gastrointestinal symptoms and gastrointestinal hormones in IBS patients,which has no significant effects on intestinal floras and inflammatory process mediated by NLRP3 inflammasome,with good safety.

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