丹参联合水凝胶负载bFGF治疗大鼠心肌纤维化的研究  

Treatment of Myocardial Fbrosis in Rats with Salvia Miltiorrhiza Combined with Hydrogel-loaded bFGF

作　　者：李延民[1] 魏燕云 冯艳[1] 刘静[1] 王献忠[1] 刘俊法[1] 周维[1] LI Yan-min;WEI Yan-yun;FENG Yan;LIU Jing;WANG Xian-zhong;LIU Jun-fa;ZHOU Wei(Second Department of Cardiology,Handan First Hospital,Handan 056000,China)

机构地区：[1]邯郸市第一医院心内二科,河北邯郸056000

出　　处：《特产研究》2022年第6期77-82,89,共7页Special Wild Economic Animal and Plant Research

基　　金：邯郸市科技计划项目(1623208064-5);河北省卫生厅重点科技研究计划项目(20130359)。

摘　　要：本研究为探究丹参联合可降解胶原水凝胶负载碱性成纤维细胞生长因子对心肌纤维化的治疗疗效以及潜在机制,制备了一种源自细胞外基质(Extra-Cellular Matrix,ECM)的丹参联合可降解Ⅰ型胶原蛋白水凝胶负载碱性成纤维细胞因子,通过心功能评价、心重指数和组织学分析其对心肌纤维化大鼠的治疗效果。此外通过Elisa验证大鼠血液中血管紧张素Ⅱ(AngⅡ)、抗氧化酶(SOD和MDA)和心肌酶(CKMB、GOT和LDH)的水平;RT-PCR验证α-SMA、TGF-β1、TIMP-1、TIMP-2、MMP-2、MMP-9、CollagenⅠ和CollagenⅢ的mRNA表达水平。与生理盐水心肌纤维化组相比,丹参bFGF水凝胶组左心室舒张末期压(LVEDP)和心重指数明显降低,左心室收缩压(LVSP)、左心室发展压最大变化速率(±dp/dt_(max))出现明显升高;与生理盐水心肌纤维化组相比,丹参b FGF理盐水(P<0.05),但MMP-2、MMP-9、CollagenⅠ和CollagenⅢ的mRNA表达水平明显降低。丹参联合可降解Ⅰ型胶原蛋白水凝胶负载碱性成纤维细胞因子能改善大鼠的心功能,调控AngⅡ、抗氧化酶和心肌酶分泌,影响心肌细胞α-SMA、TGF-β1、TIMP和MMP的mRNA表达,从而达到调控心肌细胞中胶原的合成与分泌,抑制心肌纤维化,产生强心肌保护作用。This study was conducted to investigate the therapeutic efficacy and potential mechanism of Salvia officinalis combined with degradable collagen hydrogel loaded with basic fibroblast growth factor on myocardial fibrosis.An extra-cellular matrix(ECM)-derived salvia combined with degradable typeⅠcollagen hydrogel loaded with basic fibroblast growth factor was prepared and its therapeutic effects on myocardial fibrosis rats were analyzed by cardiac function evaluation,cardiac weight index and histology.In addition,the levels of angiotensinⅡ(AngⅡ),antioxidant enzymes(SOD and MDA)and cardiac enzymes(CKMB,GOT and LDH)were verified by Elisa.Results compared with the saline-myocardial fibrosis group,left ventricular end-diastolic pressure(LVEDP)and cardiac weight index were significantly lower in the saline-bFGF-hydrogel group,and left ventricular systolic pressure(LVSP)and maximum rate of change in left ventricular developmental pressure(±dp/dt_(max))appeared significantly higher.Compared with the saline-myocardial fibrosis group,the myocardial tissue serum ALD,antioxidant enzymes and cardiac enzymes levels were significantly lower in the saline-myocardial fibrosis group;the plasma levels of AngⅡwere significantly increased.RT-PCR results showed that compared with the saline-myocardial fibrosis group,the salineb FGF-hydrogel group showed a significant decrease in the mediumα-SMA,TGF-β1,TIMP-1 and TIMP-2 mRN@A express‘ion lervels were significantly higher(P<0.05),but the mRNA expression levels of MMP-2,MMP-9,CollagenⅠand CollagenⅢwere significantly lower.It was shown that the combination of Salvia miltiorrhiza and degradable typeⅠcollagen hydrogels loaded with basic fibroblast factors could improve the cardiac function of rats,regulate the secretion of AngⅡ,antioxidant enzymes and cardiac myosin,and affect the expression ofα-SMA,TGF-β1,TIMP and MMP mRNA in cardiac myocytes,thereby regulating the synthesis and secretion of collagen in cardiac myocytes,inhibiting myocardial fibrosis and producing str

关 键 词：心肌纤维化 Ⅰ型胶原水凝胶 碱性成纤维细胞生长因子 丹参 

分 类 号：R285[医药卫生—中药学]