淫羊藿苷抑制TGF-β1/Smad2信号通路改善压力超负荷所致的大鼠心肌纤维化  

Anti-myocardial fibrosis activity of icariin in pressure overload rats through inhibition of TGF-β1/Smad2 signal pathway

作　　者：张丽梅[1] 杨竞[1] 李意奇[1] 龚其海[1] 杨丹莉[1] 

机构地区：[1]遵义医学院药理学教研室暨贵州省基础药理重点实验室,贵州遵义563000

出　　处：《中国药理学通报》2013年第10期1422-1425,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学专项基金(No 81241142);教育部"长江学者和创新团队发展计划"(No IRT1197);贵州省科技厅社发攻关计划项目(No SY[2010]3055)

摘　　要：目的观察淫羊藿苷(icariin,Ica)对大鼠压力超负荷所诱导的心肌纤维化的干预作用,并研究其作用机制是否与Ica影响左心的转化生长因子β1(transforming growth factor-β1,TGF-β1)、Smad2的表达有关。方法 SD大鼠(n=5)随机分为假手术组、心肌纤维化模型组、Ica低、高剂量干预模型组。用腹主动脉缩窄术致压力超负荷心肌纤维化模型,Ica低、高剂量组造模后次日给予Ica 40、80 mg·kg-1(ig,qd),持续50 d。期间观察大鼠的一般情况,d 51检测左心指数;用Masson染色法观察心肌间质纤维化情况,用PCR和免疫组化法分别检测心肌TGF-β1、Smad2的mRNA和蛋白表达变化。结果压力超负荷组大鼠左室心肌纤维化程度明显,并伴左心指数增高,左室TGF-β1、Smad2 mRNA和蛋白表达均明显上升。而Ica能明显改善上述病理改变,降低TGF-β1、Smad2 mRNA和蛋白的表达。结论 Ica具有抗压力超负荷所致大鼠心肌纤维化的作用,其机制至少部分与其抑制TGF-β1/Smad2信号通路有关。Aim To investigate the effect of icariin （Ica） on myocardial fibrosis induced by pressure over- load and explore the mechanism of whether or not af- fecting expressions of TGF-β1 and Smad2 in left heart. Methods The myocardial fibrosis models were in- duced by abdominal aortic coarctation. Forty male SD rats were randomly divided into sham group （ n = 10） , pressure overload model group （n = 10）, low- and high-dose of Ica-treated group （40, 80 mg· kg^-1, n = 10）. Ica was intragastrically administered for 50 days consecutively since the next day when the models were made in Ica group. The left heart index was detected on 51 th day after the rats were sacrificed. Then, the morphological changes of the heart were observed by MASSON staining. The mRNA and protein expres- sions of TGF-β1 and Smad2 were detected by real time RT-PCR and by immunohistochemistry, respectively. Results Compared with model group, the left heart index and the left ventricular myocardial fibrosis could be markedly relieved, as well as the mRNA and pro- tein expression of TGF-β1, Smad2 in left heart tissue could be down-regulated significantly in Ica-treated groups. Conclusion Ica may exert the effect of anti- myocardial fibrosis on rats, and the mechanism is, at least partly, due to the down-regulation of the expres- sion of TGF -β1 and Smad2 in left heart tissue.

关 键 词：淫羊藿苷 压力超负荷 心肌纤维化 胶原 TGF—β1 SMAD2 

分 类 号：R-332[医药卫生] R284.1