藏红花素通过TGF-β1/CTGF信号通路对慢性心衰大鼠心肌纤维化的影响  

Impact of crocin on myocardial fibrosis in rats with chronic heart failure through TGF‑beta1/CTGF signaling pathway

作　　者：张鹏鹏 胡亚丽[2] 郝银平 刘克勤[2] 郭宁 高楚淮 ZHANG Pengpeng;HU Yali;HAO Yinping;LIU Keqin;GUO Ning;GAO Chuhuai(Zhangjiakou Drug Rehabilitation Center,Zhangjiakou 075000,Hebei,China;Dept.of Pharmacy,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,Hebei,China)

机构地区：[1]张家口市戒毒康复中心,河北张家口075000 [2]河北北方学院附属第一医院药学部,河北张家口075000

出　　处：《武汉大学学报（医学版）》2023年第7期808-813,共6页Medical Journal of Wuhan University

基　　金：2020年度河北省医学科学研究课题计划(编号:20200563)。

摘　　要：目的:通过建立慢性心衰(CHF)大鼠模型,探究藏红花素(Crocin)对CHF大鼠心肌组织纤维化的影响以及对转化生长因子-β1(TGF-β1)/结缔组织生长因子(CTGF)信号通路的调控作用。方法:采用腹主动脉缩窄法建立CHF大鼠模型,造模成功后随机分为Mod组、卡托普利(CAP)组(CAP 15 mg/kg)、Crocin-L(7.5 mg/kg)、Crocin-M(15 mg/kg)、Crocin-H(30 mg/kg)组。另取10只大鼠为假手术组(Sham组),仅开腹不结扎。药物干预结束后,超声心动仪测定左心室舒张末期内径(LVDD)、左心室收缩末期内径(LVDS)、左心室射血分数(LVEF)、左心室短轴缩短分数(LVFS);HE染色观察心肌组织病理学变化,Masson染色观察心肌组织纤维化程度,免疫组化法检测心肌组织中血管紧张素Ⅱ(AngⅡ)和Ⅰ型胶原蛋白(collagenⅠ)、Ⅲ型胶原蛋白(collagenⅢ)表达,Western Blot法检测心肌组织中TGF-β1、CTGF蛋白表达。结果:与Sham组比较,Mod组大鼠心肌细胞水肿变性,组织损伤严重,大量胶原纤维沉积,心肌组织纤维化严重,LVDD、LVDS、AngⅡ、collagenⅠ、collagenⅢ、TGF-β1、CTGF蛋白表达显著升高,LVEF、LVFS显著降低(P<0.05);与Mod组比较,CAP组和藏红花素各剂量组大鼠心肌组织损伤与心肌纤维化程度明显减轻,LVDD、LVDS、AngⅡ、collagenⅠ、collagenⅢ、TGF-β1、CTGF蛋白表达均显著降低,LVEF、LVFS显著升高(P<0.05),且Crocin各剂量组间具有剂量依赖性(P<0.05);Crocin-H组上述指标的变化与CAP组比较差异无统计学意义(P>0.05)。结论:藏红花素可通过调节TGF-β1/CTGF信号通路的表达,抑制心肌纤维化,保护CHF大鼠。Objective:To establish a chronic heart failure(CHF)rat model,and to explore the impact of cro‑cin on myocardial tissue fibrosis in CHF rats and its regulation on transforming growth factor‑β1(TGF‑β1)/connective tissue growth factor(CTGF)signaling pathway.Methods:The CHF rat model was established by abdominal aortic coarctation method.After successfully modeling,the rats were randomly grouped into Mod group,captopril group(CAP group,captopril 15 mg/kg),and Crocin‑L(7.5 mg/kg),Crocin‑M(15 mg/kg)and Crocin‑H(30 mg/kg)groups,with 10 in each group.Anoth‑er 10 rats were taken as sham operation group(Sham group),and only performed laparotomy without ligation.After drug intervention,echocardiography was applied to measure left ventricular end‑diastolic diameter(LVDD),left ventricular end‑systolic diameter(LVDS),left ventricular ejec‑tion fraction(LVEF),and left ventricular short‑axis fractional shortening(LVFS);HE staining was ap‑plied to observe the myocardial histopathological changes,Masson staining was applied to observe the degree of myocardial fibrosis,immunohistochemistry was performed to detect the expression levels of angiotensinⅡ(AngⅡ),collagenⅠand collagenⅢin myocardial tissue,and Western blot method was carried out to detect the expression of TGF‑β1 and CTGF proteins in myocardial tissue.Results:Compared with those in Sham group,the myocardial cells in Mod group showed edema and degenera‑tion,tissue damage was serious,a large amount of collagen fiber deposition was found and myocardial tissue fibrosis was serious,LVDD,LVDS,the protein expression of AngⅡ,collagenⅠ,collagenⅢ,TGF‑β1,and CTGF were significantly increased,while LVEF and LVFS were significantly de‑creased(P<0.05);compared with those in Mod group,the myocardial tissue damage and myocardial fibrosis of the rats in the CAP group and the crocin groups were significantly reduced,LVDD,LVDS,the protein expression of AngⅡ,collagenⅠ,collagenⅢ,TGF‑β1 and CTGF were signifi‑cantly decreased(P<0.05),w

关 键 词：慢性心力衰竭 藏红花素 心肌纤维化 转化生长因子‑β1 结缔组织生长因子 

分 类 号：R285.5[医药卫生—中药学]