中国药房2025，Vol.36Issue(8)：920-925,6.DOI:10.6039/j.issn.1001-0408.2025.08.05
乌司他丁改善顺铂致心肌损伤的作用及机制
Improvement effects and mechanism of ulinastatin on cisplatin-induced myocardial injury
摘要
Abstract
OBJECTIVE To investigate the improvement effects and potential mechanism of ulinastatin(UTI)on cisplatin(CP)-induced myocardial injury.METHODS Rabbits were used as study subjects and randomly divided into blank group(normal saline 2 mL/d,for consecutive 7 d),CP group(150 mg/m2,on the 1st and 4th day),UTI low-dose/high-dose group(UTIL/UTIH group,UTL 25 000 or 50 000 IU/kg,once a day,for consecutive 7 d),c-Jun N-terminal kinase(JNK)inhibitor group(JNKi group,SP600125 15 mg/kg,on the 1st and 4th day+CP 150 mg/m2,on the 1st and 4th day+normal saline 2 mL/d,on the other 5 days).Except for the blank group,rabbits in the other groups were injected with relevant medicine and/or normal saline via a marginal ear vein on one side.The serum level of cardiac troponin Ⅰ(cTnⅠ)in rabbits on the 1st and 8th days of the detection experiment,as well as the levels of superoxide dismutase(SOD),glutathione(GSH)and malondialdehyde(MDA)in myocardial tissue on the 8th day of the experiment,were all measured in each group.The pathological changes and myocardial cell apoptosis in myocardial tissue were observed,and the protein expressions of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),JNK,phosphorylated JNK(P-JNK),mitochondrial fission factor(Mff),and dynamin-related protein 1(Drp1)in myocardial tissue were all determined.RESULTS Compared with the blank group,the CP group showed significant myocardial injury.The cell apoptotic rate,the levels of cTnⅠ in serum and MDA in myocardial tissue,as well as protein expressions of Bax,JNK,p-JNK,Mff,and Drp1,were all significantly increased or up-regulated,SOD level and protein expression of Bcl-2 significantly reduced or down+regulated(P＜0.05).Compared with the CP group,the myocardial injury in rabbits from each drug treatment group showed improvement.The cell apoptosis index,the levels of cTnⅠ in serum and MDA in myocardial tissue,as well as protein expressions of Bax,JNK,p-JNK,Mff(except for UTIL group),and Drp1,were all significantly reduced or down-regulated,while SOD,GSH level and protein expression of Bcl-2 significantly increased or up-regulated(P＜0.05);moreover,the improvement in some indicators was significantly better in the UTIH group and the JNKi group compared to the UTIL group(P＜0.05).CONCLUSIONS UTI may ameliorate CP-induced myocardial injury,the potential mechanism of which may be associated with antagonizing oxidative stress and inhibiting the JNK/Mff signaling pathway.关键词
乌司他丁/顺铂/心肌损伤/JNK/Mff信号通路Key words
ulinastatin/cisplatin/myocardial injury/JNK/Mff signaling pathway分类
医药卫生引用本文复制引用
任家孚,陈鹏飞,阿荣,李婧..乌司他丁改善顺铂致心肌损伤的作用及机制[J].中国药房,2025,36(8):920-925,6.基金项目
国家自然科学基金地区科学基金项目(No.82260075) （No.82260075）
内蒙古自治区自然科学基金项目(No.2024QN08043) （No.2024QN08043）
内蒙古自治区高等学校科学研究项目(No.NJZY23143) （No.NJZY23143）
内蒙古医科大学附属医院科研项目(No.2023NYFYGG020) （No.2023NYFYGG020）
内蒙古医科大学附属医院高层次人才项目"航行系列" （）
