瓜蒌薤白半夏汤调控TGF-β1/Smads信号通路对心肌缺血模型大鼠心肌细胞外基质重构的影响  

Effect of Gualou Xiebai Banxia Tang on Regulating TGF-β1/Smads Signaling Pathway on the Extracellular Matrix Remodeling in Myocardial Ischemia Model Rats

作　　者：牛耘 谭颖颖[1] 张琪[1] NIU Yun;TAN Yingying;ZHANG Qi(Basic Medical College,Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China;Xi'an Aircraft Design Institute of AVIC Group Corporation,Xi'an 710089,China)

机构地区：[1]陕西中医药大学基础医学院,陕西咸阳712046 [2]中国航空工业集团公司西安飞机设计研究所,西安710089

出　　处：《中国中医基础医学杂志》2025年第3期456-462,共7页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金项目(81873296,82074380)。

摘　　要：目的通过观察瓜蒌薤白半夏汤对心肌缺血模型大鼠心肌组织病理变化的影响,探讨其对心肌细胞外基质(ECM)重构的干预作用。方法70只SD大鼠随机选取10只为对照组,余下大鼠造模成功后随机分为模型组,瓜蒌薤白半夏汤低、中、高剂量组及美托洛尔组,持续给药28 d。干预结束后取材,HE和Masson染色观察大鼠心肌组织病理学变化及纤维化程度;免疫组化检测α-平滑肌肌动蛋白(α-SMA)的阳性表达水平;比色法测定血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)以及乳酸脱氢酶(LDH)的含量;ELISA检测血清N-末端B型利钠肽前体(NT-proBNP)及转化生长因子(TGF)-β1的含量;Western blot法检测心肌组织TGF-β1、Smad2和Smad3蛋白相对表达水平;RT-qPCR检测COL1A1和FN m RNA表达水平。结果与模型组比较,瓜蒌薤白半夏汤高剂量组心肌组织病理显示出现不同程度改善,心肌纤维排列有序,细胞界限清晰,仍有轻微间隙增宽,并伴有少量炎性细胞浸润,胶原容积分数(CVF)显著降低(P<0.01);α-SMA阳性表达平均光密度值(MOD)显著降低(P<0.01);血清CK、CK-MB、LDH、NT-proBNP以及TGF-β1水平显著降低(P<0.01);TGF-β1、Smad2和Smad3蛋白表达水平显著降低(P<0.01);COL1A1和FN m RNA表达水平显著降低(P<0.01)。结论瓜蒌薤白半夏汤显著减轻心肌缺血模型大鼠的心肌病理形态变化和纤维化程度,改善心脏功能,其机制可能与通过调控TGF-β1/Smads信号通路抑制心肌ECM重构相关。Objective To observe the effect of Gualou Xiebai Banxia Tang on the pathological changes of myocardial tissue in rats with myocardial ischemia,and the intervention effect of Gualou Xiebai Banxia Tang on myocardial ECM remodeling.Methods Ten of the 70 SD rats were randomly selected as the control group.After successful modeling,the remaining rats were randomly divided into model group,Gualou Xiebai Banxia Tang low,medium and high dose group and metoprolol group.The treatment continued for 28 days.After the intervention,HE and Masson staining were used to observe the pathological changes and fibrosis degree of myocardial tissue in rats.The positive expression level ofα-smooth muscle actin(α-SMA)was detected by immunohistochemistry.The contents of serum creatine kinase(CK),creatine kinase isoenzyme(CK-MB)and lactic dehydrogenase(LDH)were determined by colorimetry.The levels of N-terminal pro-B-type natriuretic peptide(NT-proBNP)and transforming growth factor(TGF)-β1 were detected by ELISA.The relative expression levels of TGF-β1,Smad2 and Smad3 proteins in myocardial tissue were detected by western blot.The expression levels of COL1A1 and FN mRNA were detected by RT-qPCR.Results Compared with the model group,the myocardial histopathology of the high-dose Gualou Xiebai Banxia Tang group showed different degrees of improvement,the myocardial fibers were arranged in an orderly manner,the cell boundaries were clear,there was still a slight widening of the gap,accompanied by a small amount of inflammatory cell infiltration,and collagen volume fraction(CVF)was significantly reduced(P<0.01).The mean optical density(MOD)ofα-SMA positive expression was significantly decreased(P<0.01).The levels of serum CK,CK-MB,LDH,NT-proBNP and TGF-β1 were significantly decreased(P<0.01).The expression levels of TGF-β1,Smad2 and Smad3 protein were significantly decreased(P<0.01).The expression levels of COL1A1 and FN mRNA were significantly decreased(P<0.01).Conclusion Gualou Xiebai Banxia Tang significantly reduced the myocardial p

关 键 词：瓜蒌薤白半夏汤 缺血性心脏病 心肌成纤维细胞 心肌纤维化 心肌细胞外基质 TGF-β1/Smads信号通路 

分 类 号：R285[医药卫生—中药学]