【摘要】 目的:观察盐皮质激素受体拮抗剂螺内酯和血管紧张素Ⅱ(AngⅡ)AT1受体拮抗剂缬沙坦对自发性高血压大鼠(SHR)肠系膜微动脉形态、超微结构和Ⅰ型胶原mRNA表达的影响。方法:将18只雄性SHR随机分为三组,每组6只,其中两组分别用螺内酯20mg/kg/天、缬沙坦30mg/kg/天溶于饮水中灌胃,连续治疗13周,对照组不用药,正常饮水,并与WKY大鼠(6只)比较。鼠尾法测量大鼠动脉收缩压;应用计算机图像分析系统,计算大鼠肠系膜微动脉管壁与管腔横截面积比;用透射电镜观察大鼠肠系膜微动脉结构的变化;用RT-PCR方法检测肠系膜微动脉Ⅰ型胶原mRNA水平。结果:实验第13周末,SHR对照组血压明显高于WKY组(P<0.01);缬沙坦组和螺内酯组血压明显低于SHR对照组(P<0.01);缬沙坦组的血压与WKY组接近(P>0.05)。螺内酯组和缬沙坦组大鼠肠系膜微动脉的中膜厚度/管腔半径值及中膜面积/管腔面积值仍显著大于WKY组(P<0.05),但较SHR组明显降低(P<0.01)。透射电镜见SHR肠系膜动脉壁有大片纤维组织增生,螺内酯组和缬沙坦组肠系膜动脉壁内仅见少许纤维组织增生。螺内酯组和缬沙坦组Ⅰ型胶原mRNA水平明显低于SHR对照组(P<0.01)。结论:螺内酯和缬沙坦均能抑制SHR的Ⅰ型胶原合成,表明盐皮质激素受体和AngⅡ受体在高血压阻力血管的重塑中起着重要作用。更多还原

【Abstract】 Objective:To observe the effect of mineralocorticoid receptor antagonist and AT1 receptor antagonist on ultrastructure and the expression of typeⅠcollagen mRNA in mesenteric arteries of spontaneously hypertensive rat(SHR),and explore the pathogenesis of vascular remodeling during the development of hypertension in SHR.Method:Eighteen male SHRs were divided into three groups at random:SHR control group,valsartan group and spironolactone group.Valsartan 30 mg/kg/day、spironolactone 20 mg/kg/day were administered to rats in valsartan group and spironolactone group.Wistar Kyoto(WKY)group was given normal water during the same time.After thirteen weeks treatment,systolic blood pressure was measured with tail-tuff method.The ratios of media width to lumen radius and that of media cross-sectional area to lumen area of mesenteric micro-arteries were calculated by computer imagine analysis system.The change of vascular ultrastructure was observed by means of transmission electron microscope.Expression of type Ⅰcollagen gene mRNA in mesenteric arteries were determined by RT-PCR.Results:After thirteen weeks treatment,the blood pressure in untreated SHR group was the highest among all the groups(P<0.01).The blood pressure in valsartan group was not markedly different from that in WKY group(P>0.05).The blood pressure in spironolactone group was higher than that in WKY group and valsartan group(P<0.05).Compared with WKY group,the ratio of media width to lumen radius and that of media cross-sectional area to lumen area in mesenteric arteries treated with valsartan and spironolactone significantly increased(P<0.05),but they were lower than those in untreated SHR group(P<0.01).Under electron microscope,masses of fibrous tissue distributed in the walls of mesenteric arteries in SHR.Whereas in valsartan group and spironolactone group,there was a little of fibrous tissue in the wall.Compared with those of untreated SHR group,levels of type Ⅰcollagen gene mRNA expression in mesenteric arteries treated with spironolactone and valsartan for 13 weeks were significantly reduced(P<0.05,respectively),but compared with those of WKY normal group,they were increased(P<0.01,respectively).Conclusion:These results showed that mineralocorticoid receptor antagonist and AngⅡ AT1 receptor antagonist prevented the expression of type Ⅰcollagen mRNA expression in mesenteric arteries,and indicated that mineralocorticoid receptor play an important role in the remodeling of resistant vessel in hypertension.更多还原