氯沙坦对肾衰大鼠RAS基因表达的影响

Effect of Losartan on Expression of RAS Gene in Rats with Chronic Renal Failure

目的观察氯沙坦对肾衰大鼠肾组织肾素-血管紧张素系统(RAS)血管紧张素1型受体(AT1)、血管紧张素2型受体(AT2)、血管紧张素转化酶(ACE)及血管紧张素原(AGT)基因表达的影响,探讨RAS在慢性肾衰发生发展过程中的作用。方法复制阿霉素(ADR)慢性肾衰大鼠动物模型,随机分为模型(ADR)组和血管紧张素受体拮抗剂(ARB)氯沙坦(ADR+ARB)组,氯沙坦组给予氯沙坦灌胃,另设正常大鼠对照组。取各组大鼠肾组织,经HE染色进行形态学观察,半定量RT-PCR法检测AT1、AT2、ACE及AGT基因mRNA的转录水平。结果与对照组相比,ADR组大鼠肾小球和肾小管出现明显的病变,而ADR+ARB组病变明显减轻。与对照组相比,ADR组AT1﹑AGT和ACE基因表达上调,AT2基因表达下调;与ADR组相比,ADR+ARB组AT1和AGT基因表达下调;ADR+ARB组的AT2基因表达水平接近对照组,ACE基因表达下调,但仍高于对照组水平。结论慢性肾损伤的发生发展可能与AT1、AGT及ACE基因表达水平增高有关。

Objective To observe the effectof losartan on the expressions of Rennin-angiotensin system（RAS）genes,including AT1,AT2,angiotensin-converting enzyme（ACE）and angiotensinogen（AGT）genes,in rats with chronic renal failure（CRF）,and investigate the role of RAS in onset and progress of CRF.Methods Adriamycin（ADR）-induced rat model of CRF was copied.The model rats were divided into ADR and ADR ＋ ARB groups,and those in ADR＋ARB group were treated with losartan by oral route.Normal rats were set up as control group.The kidney tissues of rats in various groups were observed for morphology by HE staining,and determined for the transcription levels of AT1,AT2,ACE and AGT mRNAs by semi-quantitative RT-PCR.Results Compared with those in control group,significantly pathogenic changes were observed in the renal glomerulus and renal tubule of rats in ADR group.However,the pathogenic changes of rats in ADR ＋ ARB group decreased significantly as compared with those in ADR group.Compared with those in control group,the expressions of AT1,ATG and ACE genes of rats in ADR group were up-regulated,while that of AT2 was down-regulated.However,the expressions of AT1 and AGT genes in ADR ＋ ARB group were down-regulated as compared with those in ADR group.The expression level of AT2 gene in ADR ＋ ARB group showed no significant difference with that in control group.Though the expression level of ACE gene in ADR ＋ ARB group was down-regulated as compared with that in ADR group,it was still higher than that in control group.Conclusion The onset and progress of chronic renal injury might be associated with the increased expressions of AT1,AGT and ACE genes.