Study on the protective mechanism of midazolam on cardiac func-tion and angiogenesis in myocardial infarction rats by regulating the JNK/STAT3 pathway
10.12092/j.issn.1009-2501.2025.10.006
- VernacularTitle:咪达唑仑通过调控JNK/STAT3通路对心肌梗死大鼠心脏功能及促血管生成作用的保护机制研究
- Author:
Aifang LI
1
;
Dong LIANG
;
Yuanhui DAI
;
Siyu CHEN
Author Information
1. 新疆医科大学第一附属医院麻醉科,乌鲁木齐 830000,新疆
- Publication Type:Journal Article
- Keywords:
midazolam;
myocardial infarction;
rat;
cardiac function;
angiogenesis;
c-Jun N-termi-nal kinase-signal transducer and activator of tran-scription 3 pathway
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(10):1342-1350
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the protective ef-fect of midazolam(MID)on cardiac function and angiogenesis in myocardial infarction(MI)rats and its effect on c-Jun N-terminal kinase-signal trans-ducer and activator of transcription 3(JNK/STAT3)pathway.METHODS:MI rat model was established by left anterior descending coronary artery ligation method.A total of 68 rats were modeled.After ex-cluding the rats that died(n=3,mortality rate≈4.4％)or failed modeling(n=5),the 60 MI rats in-cluded in this experiment were randomly divided in-to the model group(Model group),MID low,medi-um and high dose group(1 mg/kg MID-L group,3 mg/kg MID-M group,6 mg/kg MID-H group),MID high dose+JNK activator Anisomycin group(6 mg/kg MID-H+Anisomycin group),12 rats in each group.Another 12 rats undergoing sham surgery were selected as the control group.All rats were echocardiographic and evaluated for cardiac func-tion.The myocardial tissue pathological morpholo-gy and the myocardial fibrosis degree were ob-served by hematoxylin-eosin(HE)staining and Mas-son staining.The serum myocardial injury markers[creatine kinase isoenzyme(CK-MB)and brain na-triuretic peptide(BNP)]and inflammatory factors[tumor necrosis fa ctor-α(TNF-α),interleukin-1β(IL-1β)and C-reactive protein(CRP)],myocardial tis-sue oxidative stress indicators[malondialdehyde(MDA),superoxide dismutase(SOD)and reduced glutathione(GSH)]levels were detected by enzyme-linked immunosorbent assay(ELISA).The vascular endothelial growth factor(VEGF),vascular endothe-lial growth factor receptor 2(VEGFR2),p-JNK,JNK,p-STAT3 and STAT3 proteins expression levels were detected by Protein blot method(Western blot).RE-SULTS:Compared with Control group,the myocar-dial tissue damage degree in Model group was more severe,the myocardial interstitial fibrosis de-gree was greatly deepened,the collagen volume fraction was significantly increased,the left ventric-ular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly in-creased,the left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),GSH and SOD levels were significantly de-creased,and the VEGF,VEGFR2 proteins expression levels were significantly decreased,the p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P＜0.05).Compared with Model group,with the MID dose increase,the myocardial tissue damage de-gree in MID-L,MID-M and MID-H groups was signif-icantly reduced,the myocardial interstitial fibrosis degree was reduced,the collagen volume fraction was decreased,the LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly decreased,the LVEF,LVFS,GSH and SOD levels were significantly increased,and the VEGF,VEGF2R protein expression levels were significantly in-creased,p-JNK/JNK and p-STAT3/STAT3 were signifi-cantly decreased(P＜0.05).Compared with MID-H group,the myocardial tissue damage degree in MID-H+Anisomycin group was more severe,the myocardial interstitial fibrosis degree was greatly deepened,the collagen volume fraction was signifi-cantly increased,the cardiac function was weak-ened,the oxidative stress and inflammation were aggravated,LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were increased,the LVEF,LVFS,GSH,SOD,VEGF and VEGFR2 proteins expres-sion levels were significantly decreased,p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P＜0.05).CONCLUSION:MID may improve myocardial tissue damage in MI rats by regulating JNK/STAT3 pathway,reduce oxidative stress and inflammatory response,promote angiogenesis,so as to play a role in cardiac protection.
