RAS在心房颤动患者心房纤维化中的作用

Effect of RAS in atrial tissue of atrial fibrillation in patient with rheumatic heart disease

目的:检测风湿性心脏病(风心病)心房颤动(房颤)患者血清血管紧张素Ⅱ(AngⅡ)水平、右心房组织内血管紧张素Ⅱ受体1(AT1-R)mRNA、蛋白表达水平及胶原含量,探讨肾素-血管紧张素系统(RAS)在风心病房颤患者心房纤维化中的作用及意义。方法:将38例风心病接受换瓣手术者于术中获取的右心耳分为3组,其中窦性心律组8例,阵发性房颤组10例,持续性房颤组20例,先天性心脏病窦性心律接受开胸手术患者10例为对照组。对各组心房组织应用羟脯氨酸含量测定法及Masson染色检测胶原含量及分布;应用ELISA法检测血清AngⅡ;应用免疫组织化学技术检测AT1-R蛋白表达及分布;应用RT-PCR检测AT1-R mRNA水平,应用Western blot检测AT1-R的蛋白表达。结果:与窦性心律组相比,血清AngⅡ水平及心房组织胶原容积分数在阵发性房颤组和持续性房颤组均显著增加(均P<0.05);AT1-R主要表达在心房肌细胞。与窦性心律组相比,AT1-R mRNA在持续性房颤组显著减少(P<0.05),AT1-R蛋白表达在阵发性房颤组和持续性房颤组均显著减少(均P<0.05)。患者血清AngⅡ水平与心房胶原含量呈正相关(P<0.05),AT1-RmRNA和蛋白表达与心房胶原含量呈负相关(P<0.05)。结论:血清AngⅡ水平参与心房纤维化胶原代谢;心房组织中AT1-R mRNA表达及蛋白水平与心房纤维化程度呈负相关。

Objective：To investigate the level of serum AngⅡ and the expression of AT1-R in atrial tissue of the patient with rheumatic heart disease（RHD）,and the effects of RAS on rheumatic atrial myocardial fibrosis.Method：Of 38 RHD patients,8were with sinus rhythm,10were with paroxysm atrial fibrillation（pAF）,and 20were with chronic AF（cAF）（≥6months）.The right atrial muscle specimens were obtained during the operation of mitral valve replacement.10congenital heart disease patients with sinus rhythm undergoing cardiac surgery were as the control group.The collagen content and distribution of myocardium specimens were obtained by hydroxyproline detection and Masson stain.The level of serum AngⅡ was examined by ELISA.The expression and distribution of AT1-R were examined by immunohistochemical stain.The mRNA content of AT1-R was measured by RT-PCR.Proteins of AT1-R was measured by western blot.Result：The level of serum AngⅡ and collagen content of atrial tissuein pAF group and cAF group were higher than that in sinus rhythm group（P0.05）.AT1-R was stained major in myocardium cells.The level of AT1-R expression and mRNA content in cAF group were lower than that in sinus rhythm group（P0.05）;The protein expression degree of AT1-R in pAF group and cAF group were decreasing than that in sinus rhythm group（P0.05）.The level of serum AngⅡin patients with RHD was positively correlation with the collagen content（P0.05）.AT1-R mRNA content and the protein expression were negative correlation with the collagen content（P0.05）.Conclusion：AngⅡlevel in serum may be involved in collagen metabolism in atrial fibrosis.In atrial tissue,AT1-R mRNA or protein levels suggest a negative correlation with the degree of atrial fibrosis.