摘要
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5×109Pfu/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。
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 nullAd 5 in A group and 5 × 10 9 Pfu / ml Ad 5-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 intraventricular pressure.HGF levels were measured by ELISA assay and AngⅡ 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,AT1R,Bcl-2 and Bax were detected by Western blot.Results Compared with the positive control group,LVEDP and-dp / dt max in Ad-HGF group were both lower,while ＋ dp / dt max was higher（P 〈 0.05）.Myocardial HGF and Bcl-2 which resisted apoptosis were signicantly higher（P 〈 0.05）,while AngⅡ,AT1R and Bax level and cardiocyte 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 AngⅡ,AT1R,Bax and up-regulating Bcl-2 and the ratio of Bcl-2 / Bax,and reducing pressure of the left ventricular wall.
出处
《安徽医科大学学报》
CAS
北大核心
2012年第8期915-919,共5页
Acta Universitatis Medicinalis Anhui
基金
安徽省自然科学基金项目资助(编号:11040606M157
11040606Q20)
安徽省高等学校省自然科学研究项目(编号:KJ2011Z213)
