Objective To investigate the effects of recombined adenovirus- hepatocyte growth factor ( Ad-HGF )with local myocardial injection on apoptosis of spontaneously hypertensive rats ( SHR ). Methods Thirty SHR served as myocardial fibrosis models, 6 of which were randomly selected as positive controls and the rest were randomly divided into adenovirus group and Ad-HGF group. The left ventricular walls were injected with 0. 1 ml null-Ad5 in A group and 5 x 109 Pfu/ml Ad5-HGF in Ad-HGF at 5 points after thoracotomy. 8 rats survived in adenovirus group and 10 rats in Ad-HGF group, which 6 rats were sacrificed at the 4th week after measured left intravent-ricular pressure. HGF levels were measured by ELISA assay and Ang II concentration was detected by radio-immunity assay. Immunohistochemistry method and image analysis system were adopted to analyze Bcl-2 and Bax level in myocardium. Cadiocyte apoptotic index was detected by TUNEL. Expressions of anti-apoptotic protein HGF, Ang II , ATI R, Bcl-2 and Bax were detected by Western blot. Results Compared with the positive control group, LV-EDP and - dp/dtmax in Ad-HGF group were both lower, while + Ap/6tmax was higher( P <0. 05 ). Myocardial HGF and Bcl-2 which resisted apoptosis were signicantly higher( P < 0. 05 ), while Ang II , ATI R and Bax level and car-diocyte apoptosis index were significantly lower( P < 0. 05 ). Conclusion Ad-HGF therapy can reduce left ventricle apoptosis index of SHR. The mechanism of HGF may be related with inhibiting Ang II , ATI R, Bax and up-regulating Bcl-2 and the ratio of Bcl-2/Bax, and reducing pressure of the left ventricular wall.%目的 探讨局部心肌注射重组腺病毒-肝细胞生长因子(Ad-HGF)对自发性高血压大鼠(SHR)心肌细胞凋亡的影响.方法 30只SHR为心肌纤维化模型,随机抽取6只作为阳性对照组,其余24只再随机平分为腺病毒组、Ad-HGF组.腺病毒组、Ad-HGF组SHR开胸,左心室壁5点分别注射0.1 ml null-Ad5和5×109 Pfu/ml Ad5-HGF,术后两组分别存活8只和10只,于4周时处死其中6只.处死前测量左心室内压,ELISA法测定心肌HGF浓度,放射免疫法检测血管紧张素Ⅱ(AngⅡ)浓度,免疫组化法及图像分析系统分析心肌Bcl-2和Bax水平,心肌细胞凋亡指数检测采用TUNEL,Western blot法测定HGF、AT1R、Bcl-2和Bax的蛋白表达.结果 与阳性对照组相比,Ad-HGF组左室内压表现为左心室舒张末压(LVEDP)下降(P<0.05)、左心室压力最大下降速度(-dp/dtmax)下降(P<0.05),左心室压力最大上升速度(+dp/dtmax)上升(P<0.05).心肌HGF、抗细胞凋亡蛋白Bcl-2显著升高(P<0.05);AngⅡ、AT1R与促细胞凋亡基因Bax水平,心肌细胞凋亡指数明显降低(P<0.05).结论 Ad-HGF可以降低SHR左心室心肌细胞凋亡指数,其作用机制可能与HGF抑制AngⅡ、AT1R、Bax,上调Bcl-2,提高Bcl-2/Bax比例,同时降低心室壁压力有关.
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