钩藤生物碱对自发性高血压大鼠胸主动脉平滑肌细胞凋亡和增殖的影响

摘要

目的 研究钩藤碱、异钩藤碱和钩藤总生物碱对SHR胸主动脉平滑肌细胞凋亡和增殖的影响.方法 分别给予SHR钩藤碱、异钩藤碱和钩藤总生物碱,并以Wistar大鼠作为正常对照.用流式细胞仪检测胸主动脉平滑肌细胞凋亡,用免疫组化法检测胸主动脉Bcl-2、Bax、c-myc、c-fos蛋白表达,采用原位杂交法检测胸主动脉平滑肌细胞PDGF mRNA及凋亡平滑肌细胞mRNA的表达.结果 钩藤碱、异钩藤碱和钩藤总生物碱均能促进SHR胸主动脉平滑肌细胞凋亡,增强Bax蛋白及凋亡平滑肌细胞mRNA表达,抑制c-fos蛋白、c-myc蛋白和PDGF-B mRNA表达；其中异钩藤碱能抑制胸主动脉Bcl-2表达.结论 钩藤碱、异钩藤碱和钩藤总生物碱可能通过调节原癌基因Bcl-2和Bax蛋白表达,促进自发性高血压大鼠动脉平滑肌细胞凋亡,并能通过抑制c-fos蛋白、c-myc蛋白和PDGF-B mRNA表达途径抑制自发性高血压大鼠胸主动脉细胞增殖,从而改善胸主动脉壁重塑.%Aim To study the influence of rhynchophylline, isorhynchophylline and uncuria alkaloids on SHR aorta smooth muscle cell apoptosis and proliferation.Methods SHRs were grouped and given rhynchophylline, isorhynchophylline and uncaria alkaloids respectively.In addition, Wistar rats were selected as normal control group.Apoptosis of aortic smooth muscle cells was measured by flow cytometry, protein expression of thoracic aortic such as Bcl-2, Bax, c-myc and c-fos were detected by immunohistochemical method and detect PDGF mRNA of thoracic aortic smooth muscle cells and the mRNA expression of apoptosis smooth muscle cell by in situ hybridization method.Results Rhynchophylline, isorhynchophylline and uncaria alkaloids could promote smooth muscle cell apoptosis in thoracic aortic of SHR.They not only advance Bax protein expression and the mRNA expression of apoptosis smooth muscle cell, but also inhibit protein expression of c-fos, c-myc and PDGF-B mRNA.Especially isorhynchophylline inhibited Bcl-2 expression in thoracic aortic.Conclusions Uncaria extract may promote apoptosis in SHR arteries by regulating the protein expression of Bcl-2 and Bax.And they may inhibit the thoracic aorta abnormal cellular proliferation in hypertension by restraining protein expression of c-fos, cmyc and PDGF-B mRNA, so as to improve the thoracic aorta wall reconstruction.