前列地尔注射液对阿霉素诱导的大鼠心肌纤维化的防治作用  

Preventive Effects of Alprostadil on Myocardium against Doxorubicin Induced Myocardial Fibrosis in Rats

作　　者：熊美红 张志 XIONG Meihong;ZHANG Zhi(Dalian Third People's Hospital,Dalian 116033,Liaoning,China)

机构地区：[1]大连市第三人民医院,大连116033

出　　处：《中西医结合心脑血管病杂志》2025年第8期1160-1164,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：辽宁省科学技术项目(No.2012225019)。

摘　　要：目的:探讨不同剂量前列地尔对阿霉素诱导的大鼠心肌纤维化的防治作用及相关机制。方法:60只SD大鼠随机分为4组:正常对照组(NC组)、阿霉素心肌病模型组(ACM组)、低剂量前列地尔组(LA组)、高剂量前列地尔组(HA组),每组15只。NC组不外加干预措施,其余组给予阿霉素2.5 mg/kg每周1次腹腔注射,连续6周,累计总剂量达15 mg/kg,停药2周。实验开始后5 d LA组于另一区域腹腔内注射前列地尔1.25μg/kg,连续8周。实验开始后5 d HA组于另一区域腹腔内注射前列地尔5.0μg/kg,连续8周。实验结束后进行超声检测评价其心功能,检测丙二醛(MDA)、谷胱甘肽(GSH)含量。电镜下观察Masson染色心肌间质胶原纤维沉积情况。蛋白免疫印迹法检测心肌组织中转化生长因子-β_(1)(TGF-β_(1))和转录因子Smad2磷酸化水平的表达情况。结果:ACM组MDA明显高于NC组,GSH明显低于NC组(P<0.05);HA组与LA组MDA明显低于ACM组,GSH明显高于ACM组(P<0.05)。与NC组相比,ACM组左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、心脏指数(H/B)、左室质量指数(LVMI)均明显升高(P<0.01)。与ACM组相比,LA组和HA组LVSP、LVEDP、H/B、LVMI均明显下降(P<0.01)。与NC组相比,ACM组大鼠心肌组织中TGF-β_(1)和转录因子Smad2磷酸化水平明显升高(P<0.01);与ACM组相比,LA组和HA组大鼠心肌组织中TGF-β_(1)和p-Smad2的蛋白表达水平均明显下降(P<0.01);与NC组相比,ACM组大鼠心肌组织中Smad7蛋白表达水平下降,而在LA组和HA组中表达升高(P<0.01)。结论:前列地尔通过抑制心肌组织中由TGF-β_(1)/p-Smad2介导的信号传导通路,逆转阿霉素诱导的大鼠心肌纤维化过程。Objective:To investigate the protective effect of different doses of alprostadil on myocardiun against adriamycin-induced myocardial fibrosis in rats and its mechanism.Method:Sixty SD rats were randomly divided into 4 groups:normal control group(NC group),adriamycin group(ADM group),low-dose alprostadil group(LA group),and high-dose alprostadil group(HA group).The NC group did not received additional intervention measures.And the remaining groups were given an intraperitoneal injection of Adriamycin with a dose of 2.5 mg/kg once a week for 6 consecutive weeks.The drug was discontinued for 2 weeks.Alprostadil 1.25μg/kg was intraperitoneally injected into the other region 5 days after the start of the experiment in LA group for 8 consecutive weeks.Alprostadil 5.0μg/kg was intraperitoneally injected into the other region 5 days after the start of the experiment for 8 weeks in HA group.At the end of the experiment,echocardiography was used to evaluate the cardiac function,and the contents of malondialdehyde(MDA)and glutathione(GSH)were detected.Masson staining was used to observe the deposition of collagen fibers in myocardial interstitium under electron microscope.Western Blot was used to detect the expression of transforming growth factor-β_(1)(TGF-β_(1))and phosphorylated Smad2 in myocardial tissue.Results:MDA in ACM group was significantly higher than that in NC group,GSH was significantly lower than that in NC group(P<0.05).MDA was significantly lower and GSH was significantly higher in HA and LA groups than that in ACM group(P<0.05).Compared with ACM group,the levels of left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),cardiac index(H/B),and left ventricular mass index(LVMI)in ACM group significantly increased(P<0.01).Compared with the ACM group,the levels of LVSP,LVEDP,H/B and LVMI in LA group and HA group significantly decreased(P<0.01).Compared with the NC group,the levels of TGF-β_(1) and phosphorylated transcription factor Smad2 in the myocardial tissue of the ACM

关 键 词：心肌纤维化 前列地尔 阿霉素 实验研究 

分 类 号：R542.2[医药卫生—心血管疾病]