丹酚酸B抗心肌纤维化的机制研究  

Study on the Mechanism of Anti-myocardial Fibrosis of Salvianolic Acid B

作　　者：罗红[1,2] 王春花 赵玲璐[1] 杨宇 陈世平[1] 徐旖旎[1] 杨红宇[2] 沈祥春 

机构地区：[1]贵州医科大学贵州省高等学校天然药物药理与成药性评价特色重点实验室,贵阳550025 [2]贵州医科大学实验动物中心,贵阳550025

出　　处：《中国药房》2017年第28期3900-3903,共4页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81560588);贵州省科技合作计划项目(No.黔科合LH字[2016]7356号);贵州省科学技术基金项目(No.黔科合JZ字[2015]2002号);贵州省高层次创新型人才培养项目(No.黔科合人才[2015]4029号);贵州医科大学2015年高等学校大学生创新创业训练计划项目(No.201510660007)

摘　　要：目的:研究丹酚酸B(Sal B)对血管紧张素Ⅱ(AngⅡ)诱导的心肌成纤维细胞增殖、Ⅲ型胶原分泌及基质金属蛋白酶9(MMP-9)、Smad2/3、Smad7蛋白表达的影响,探讨其抗心肌纤维化的作用机制。方法:将细胞分为空白对照组(培养液)、AngⅡ模型组和Sal B低、中、高浓度组(12.5、25、50μmol/L),用空白或含药培养液培养细胞1 h后,除空白对照组外的其余各组均加入1μmol/L的AngⅡ诱导细胞增殖,共同作用24 h。分别采用MTT法和苏木精-伊红染色法考察Sal B对细胞增殖的影响;采用Western blot法检测Sal B对细胞Ⅲ型胶原、MMP-9、Smad2/3、Smad7蛋白表达的影响。结果:与空白对照组比较,AngⅡ模型组细胞明显增殖,Ⅲ型胶原、MMP-9、Smad2/3蛋白表达明显增强,Smad7蛋白表达明显减弱,差异均有统计学意义(P<0.05);与AngⅡ模型组比较,Sal B各浓度组细胞的增殖均受到抑制,Ⅲ型胶原、MMP-9、Smad2/3蛋白表达均减弱,Smad7蛋白表达均增强,除Sal B低、中浓度组细胞Ⅲ型胶原与Sal B高浓度组细胞Smad2/3蛋白表达变化不显著外,其余各指标差异均有统计学意义(P<0.05)。结论:Sal B抗心肌纤维化的作用可能与抑制心肌成纤维细胞的增殖,下调Ⅲ型胶原、MMP-9、Smad2/3蛋白表达和上调Smad7蛋白表达有关。OBJECTIVE：To study the effects of salvianolic acid B（Sal B）on angiotensin Ⅱ（Ang Ⅱ）-induced cardiac fibro-blast proliferation,secretion of type Ⅲ collagen,protein expressions of matrix metalloproteinase 9 （MMP-9）,Smad2/3,Smad7, and explore its mechanism of anti-myocardial fibrosis. METHODS：Cells were divided into blank control group（culture medium） Ang Ⅱ model group,Sal B low-dose,medium-dose,high-dose groups （12.5,25,50 μmol/L）. After cultured 1 h by blank or drug-containing culture,except for blank control group,cells in other groups were added 1 μmol/L Ang Ⅱ to induce proliferation. for 24 h. MTT method and hematoxylin-eosin staining method were adopted investigate the effect of Sal B on proliferation. Western blot method was adopted to detect the effects of Sal B on protein expressions of type Ⅲ collagen,MMP-9,Smad2/3,Smad7. RE-SULTS：Compared with blank control group,cells in Ang Ⅱ model group were significantly proliferated,protein expressions of type Ⅲ collagen,MMP-9,Smad2/3 were obviously enhanced,protein expression of Smad7 was obviously weakened,with statisti-cal significances（P〈0.05）. Compared with Ang Ⅱ model group,the cell proliferation in Sal B groups were inhibited,protein ex-pressions of typeⅢcollagen,MMP-9,Smad2/3 were weakened,while protein expression of Smad7 was enhanced. Except the pro-tein expression of type Ⅲ collagen in Sal B low-dose and medium-dose groups,the protein expression of Smad2/3 in Sal B high-dose group did not change significantly,other indexes had statistical significances（P〈0.05）. CONCLUSIONS：The anti-myo-cardial fibrosis effect of Sal B may be associated with inhibiting the proliferation of cardiac fibroblasts,down-regulating protein ex-pressions of typeⅢcollagen,MMP-9,Smad2/3 and up-regulating protein expression of Smad7.

关 键 词：丹酚酸B 心肌成纤维细胞 Ⅲ型胶原 基质金属蛋白酶9 转化生长因子β1信号通路 

分 类 号：R541[医药卫生—心血管疾病]