西罗莫司与依那普利对大鼠心房纤维化的影响

Effects of sirolimus and enalapril on atrial fibrosis in rats

目的初步探讨西罗莫司与依那普利对异丙肾上腺素诱导的心房纤维化的影响及其可能机制。方法雄性Wistar大鼠40只,随机分为4组,即正常对照组、模型组、西罗莫司干预组和依那普利治疗组,每组10只。经大剂量皮下注射盐酸异丙肾上腺素建立大鼠心房纤维化模型,后两组分别给予西罗莫司及依那普利灌胃治疗,实验2周末处死大鼠取心肌组织,放射免疫法检测血管紧张素Ⅱ(AngⅡ);常规HE和Masson染色法观察心房纤维化程度;免疫组织化学染色及Western印迹法检测低氧诱导因子-1α(HIF-1α)和基质金属蛋白酶-9(MMP-9)在大鼠心房纤维化组织中的表达。结果与正常对照组相比,模型组中AngⅡ含量明显升高(P<0.01),而依那普利治疗组AngⅡ较模型组明显降低(P<0.01);与模型组相比,西罗莫司和依那普利治疗组心房纤维化程度明显减轻(P<0.01);免疫组织化学法及Western印迹法检测结果显示,与正常对照组相比,模型组心肌组织中HIF-1α和MMP-9的表达明显升高(P<0.01),而西罗莫司和依那普利治疗组则较模型组明显降低(P<0.01),且与纤维化程度呈正相关(P<0.01);心肌组织中HIF-1α与MMP-9表达也呈正相关(P<0.01)。结论心肌组织中,AngⅡ、HIF-1α和MMP-9均参与大鼠心房纤维化的形成,而西罗莫司与依那普利可能通过作用于不同靶点,改善心房纤维化程度。

Objective To explore the effects of sirolimus and enalapril on atrial fibrosis of rats induced by isoproterenol. Methods Forty male Wistar rats were randomly divided into control group, isoproterenol model group [ isoproterenol 5 mg/（ kg · d） for 7 d], 3 mg/（ kg · d） sirolimus and 10 mg/（ kg · d） enalapril treatment groups. Mice were sacrificed after 2 weeks. The angioten- sin I1 （Ang I[ ） content in myocardial tissue was measured by radioimmunoassay, atrial fibrosis was determined on HE and Masson stained heart sections, and the expression of HIF-1 a and matrix metalloproteinases -9 （MMP-9） were detected by immunohistochemistry and Western blotting. Results Compared with control group, the content of Ang II increased in model group（P 〈 0. 01 ）, but in enal- april treatment group it was significantly lower than that in the model and Western bohting groups（P 〈 0. O1 ） ; the expression of HIF- lc~ and MMP-9 in myocardium increased in model group（ P 〈 0. O1 ）, while the degree of atrial fibrosis was significantly lower in siroli- mus group and enalapril group than in model group（P 〈 O. 01 ） ; and the expressim of HIF-1 ct and MMP-9 decreased in sirolimus and enalapril groups （P 〈 O. O1 ）. Conclusion Ang Ⅱ , HIF-1 a and MMP-9 in myocardial tissue may be involved in the formation of atrial fibrosis. Sirolimus and enalapril can attenuate atrial fibrosis by acting on different targets.