基于TGF-β1/p38MAPK/CREB信号通路探讨心衰康胶囊对糖尿病大鼠心肌纤维化的改善作用  

Improvement Effect of Xinshuaikang Capsule(心衰康胶囊)on Myocardial Fibrosis in Diabetes Rats Based on TGF-β1/p38MAPK/CREB Signal Pathway

作　　者：张晓晋 张常喜 张亚平 马力 张雄慧 闫文瑞 ZHANG Xiaojin;ZHANG Changxi;ZHANG Yaping;MA Li;ZHANG Xionghui;YAN Wenrui(Pulmonary Department of Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine,Yinchuan 750021,Ningxia,China;Clinical College of Traditional Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730020,Gansu,China;College of Traditional Chinese Medicine,Ningxia Medical University,Yinchuan 750001,Ningxia,China)

机构地区：[1]宁夏回族自治区中医医院肺病科,宁夏银川750021 [2]甘肃中医药大学中医临床学院,甘肃兰州730020 [3]宁夏医科大学中医学院,宁夏银川750001

出　　处：《辽宁中医杂志》2024年第8期186-189,I0003,共5页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81960810)。

摘　　要：目的探究心衰康胶囊是否通过调控TGF-β1/p38MAPK/CREB信号通路改善糖尿病大鼠心肌纤维化。方法清洁SPF级雄性大鼠32只,随机分为对照组、模型组、心衰康胶囊组(1.0 g·kg^(-1)·d^(-1))、缬沙坦组(30 mg·kg^(-1)·d^(-1))。除对照组外,按30 mg/kg体质量腹腔注射浓度为1 mg/mL的链脲佐菌素(STZ)制备糖尿病模型大鼠,对照组和模型组均0.9%氯化钠溶液灌胃。采用苏木素-伊红(HE)染色观察糖尿病大鼠心肌组织病理变化;免疫组织化学法检测转化生长因子-β1(TGF-β1)蛋白表达水平;酶联免疫吸附剂测定(ELISA)法检测大鼠TGF-β1、大鼠B细胞淋巴瘤因子2(Bcl-2)、半胱氨酸蛋白酶3(caspase-3)蛋白水平;Western Blot法检测心肌组织中TGF-β1、磷酸化-丝裂原活化蛋白激酶p38抗体(p-p38MAPK)、cAMP反应元件结合蛋白(cAMP response element binding protein,CREB)蛋白表达水平的变化。结果与对照组比较,模型组大鼠心肌排列紊乱,组织肿胀,有大量炎性细胞浸润,Bcl-2、p-CREB蛋白表达水平明显降低(P<0.01),TGF-β1、Caspase-3、p-p38 MAPK蛋白表达明显升高(P<0.05,P<0.01);与模型组相比,心衰康胶囊组大鼠心肌纤维排列较整齐,炎性浸润减少,组织间隙无明显水肿,TGF-β1、p-p38 MAPK、Caspase-3蛋白表达水平明显降低(P<0.01,P<0.05),p-CREB、Bcl-2蛋白表达水平升高(P<0.05,P<0.01)。结论心衰康胶囊可抑制糖尿病大鼠的心肌纤维化以及细胞凋亡,其改善作用可能与调控TGF-β1/p38MAPK/CREB信号通路有关。Objective To explore whether Xinshuikang Capsule(心衰康胶囊)can improve myocardial fibrosis in diabetic rats by regulating transforming growth factor-β1(TGF-β1)/mitogen-activated protein kinase p38 antibody(p38MAPK)/cAMP response element binding protein(CREB)signaling pathway.Methods Thirty-two SPF male rats were randomly divided into control group,model group,Xinshuaikang Capsule group(1.0 g·kg^(-1)·d^(-1))and valsartan group(30 mg·kg^(-1)·d^(-1)).In addition to the control group,streptozotocin(STZ)with a concentration of 1 mg/mL was intraperitoneally injected at a body mass of 30 mg/kg to prepare diabetes model rats.Both the control group and the model group were given normal saline by gavage.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of myocardial tissue in diabetic rats.The immunohistochemical method was used to detect the protein expressions of TGF-β1.The enzyme-linked immunosorbent assay(ELISA)was used to detect the protein levels of TGF-β1,B-cell lymphoma factor 2(Bcl-2)and cysteine protease 3(Caspase-3).Western Blot was used to detect the expressions of TGF-β1,phosphorylation-p38MAPK(p-p38MAPK)and CREB.Results Compared with those of the control group,the myocardial arrangement of the rats in the model group was disordered,with tissue swelling and a large amount of inflammatory cell infiltration.The expression levels of Bcl-2 and p-CREB proteins were significantly reduced(P<0.01),and the expressions of TGF-β1,Caspase-3 and p-p38MAPK proteins were significantly increased(P<0.05,P<0.01).Compared with those of the model group,the myocardial fibers of the rats in the Xinshuaikang Capsule group were more neatly arranged and the inflammatory infiltration was reduced.There was no obvious edema in the interstitial space.The protein expression levels of TGF-β1,p-p38MAPK and Caspase-3 decreased significantly(P<0.01,P<0.05),while the protein expression levels of p-CREB and Bcl-2 increased(P<0.05,P<0.01).Conclusion Xinshuaikang Capsule can inhibit myocardial fibrosis and

关 键 词：心衰康胶囊 糖尿病心肌病 心肌纤维化 大鼠 TGF-β1/p38MAPK/CREB信号通路 

分 类 号：R255.4[医药卫生—中医内科学]