α_1-肾上腺素受体在缺氧性肺动脉平滑肌细胞增殖中的作用  

Role of α_1 adrenoceptor in proliferation of hypoxic pulmonary artery smooth muscle cells

作　　者：姚香兰[1,2,3] 薛全福[1,2] 赵琪平[1,2] 

机构地区：[1]中国医学科学院基础医学研究所 [2]中国协和医科大学基础医学院生理和病理生理学系,北京100005 [3]美国国立卫生院心肺血研究所

出　　处：《中国病理生理杂志》2011年第6期1187-1192,共6页Chinese Journal of Pathophysiology

基　　金：国家医学科技攻关资助项目(No.85-915-03-06)

摘　　要：目的:探讨肾上腺素α1受体(α1AR)及β2受体(β2AR)在缺氧性肺动脉平滑肌细胞(PASMCs)增殖中的作用及分子机制。方法:用贴块法培养新生牛肺动脉平滑肌细胞至第6代,并作免疫组化染色鉴定。细胞在6.6%O2环境中常压缺氧6、12、24 h,用[3H]-TdR掺入法反映DNA合成测定PASMCs的增殖,用Fura-2/AM测定胞内Ca2+浓度。用Northern blotting法观察PASMCs的c-fos、c-myc基因表达和α1AR mRNA、β2AR mRNA的变化。加用不同的受体激动剂和抑制剂,探讨α1AR被激活和抑制后,以及β2AR激活后对上述变化的影响。结果:单纯缺氧,PASMCs DNA合成即明显增加,α1AR激活后,增加更明显;而α1AR抑制后,明显降低(P<0.01)。β2AR激活时无明显变化。缺氧后胞内游离钙浓度也增高(P<0.01),PASMCs上c-fos和c-myc基因表达增强(P<0.05),α1AR mRNA和β2AR mRNA水平均显著增高(P<0.01)。结论:结果提示缺氧刺激PASMCs,使胞内钙浓度增加,c-fos和c-myc基因表达增强,引起PASMCs增殖,这一增殖是通过α1AR介导的,但β2AR不起主要作用。缺氧时α1AR增多,既促进肺血管收缩,又加强细胞增殖,在缺氧性肺血管收缩和肺血管重建导致的肺动脉高压中起一定的作用。AIM：To investigate the role of α1 and β2 adrenoceptors（α1AR and β2AR） in the proliferation of hypoxic pulmonary artery smooth muscle cells（PASMCs）.METHODS： PASMCs were isolated by an explant method from neonatal bovine pulmonary arteries.The cultured PASMCs were exposed to 6.6% O2 for 6 h,12 h and 24 h.The method of -TdR incorporation was used to measure the proliferation of PASMCs. i was assayed with Fura-2/AM.The mRNA expression of α1AR, β2AR,c-fos and c-myc was determined by Northern blotting.The effects of activation of α1AR and β2AR,and inhibition of α1AR on the above indexes were observed by treating PASMCs with different AR agonists and antagonists under hypoxic condition.RESULTS： Significant increase in TdR incorporation in hypoxic PASMCs with α1AR activation was observed,and marked decrease in that was induced by α1AR inhibition. However,no significant change was found after β2AR activation.[Ca2＋]i,the mRNA expression of c-fos,c-myc,α1AR and β2AR in PASMCs were increased after hypoxia.CONCLUSION： Hypoxia induces the increase in i and mRNA expression of c-fos and c-myc,leading to the proliferation of PASMCs.The hypoxic proliferation of PASMCs is intervened by α1AR,but not β2AR.The remodeling of pulmonary arteriole and pulmonary hypertension may be involved in the processes of pulmonary arteriole constriction and proliferation induced by hypoxia through up-regulation of α1AR.

关 键 词：缺氧 受体 肾上腺素能 细胞增殖 肺动脉平滑肌细胞 

分 类 号：R363[医药卫生—病理学]