辛伐他汀及洛沙坦对糖尿病鼠肾nephrin基因表达的影响.docVIP

摘 要 目的：探讨羟甲基戊二酸单酰辅酶A还原酶抑制剂Simvastatin及血管紧张素Ⅱ受体拮抗剂Losartan对糖尿病鼠肾nephrin基因表达的影响。 方法：选用成年雄性SD大鼠，随机分为正常对照组、STZ注射2周组及4周组、DM 4组及8周组、Losartan 4周组及8周组、Simvastatin 4周组及8周组，以STZ诱导DM，分别以Losartan及Simvastatin灌胃。不同病程取标本以放免法测定尿白蛋白排泄率（UAE）、尿β2－MG排泄率，测定血浆胆固醇浓度，免疫组化及荧光定量RT-PCR法定性及定量测定肾脏nephrin mRNA的表达。统计学处理采用单因数方差分析及相关分析。 结果： DM非治疗组UAE及β2-MG排泄率高于对照组（p0.01），而Losartan治疗组和Simvastatin治疗组则明显低于DM8周非治疗组（p0.01）； STZ注射后4周nephrin mRNA的表达量较对照组明显升高,且达对照组的两倍，而所有DM非治疗组nephrin mRNA的表达量则明显低于对照组、STZ注射后4周组及Losartan 8周组，其中DM8周非治疗组的表达量也较Simvastatin治疗组明显减少， Losartan 8周组nephrin的表达量高于Losartan 4周组（p0.01），而Simvastatin 4周与8周组间没有差别。 结论：（1）DM大鼠UAE及尿β2－MG排泄率均明显升高，Simvastatin及Losartan均可减少DM大鼠的UAE及尿β2－MG排泄率；（2）注射STZ 4周后，DM鼠肾nephrin mRNA表达上调50％，然而，随着高血糖状态时间的延长，表达量开始明显下降；（3）Simvastatin及Losartan均可阻断DM鼠肾nephrin mRNA表达的下调。 关键词：糖尿病肾病nephrin；Simvastatin；Losartan ABSTRACT Objective: To study the effect of 3- hydroxy-3- Methylglutaryl CoA inhibitor Simvastatin and specific antagonist of angiotensin Ⅱ receptor Losartan on the expression of nephrin gene of diabetic glomerulopathy in STZ-induced diabetic rats. Methods: Adult male SD rats were divided randomly into 9 groups:control group and the groups of 2 weeks after injected STZ, 4 weeks after injected STZ, 4 weeks after DM no treated, 8 weeks after DM no treated, 4 weeks after treated with Losartan, 8 weeks after treated with Losartan, 4 weeks after treated with Simvastatin and 8 weeks after treated with Simvastatin. The rats were induced to become diabetes by injection of STZ. The last four groups were treated orally with Simvastatin and Losartan differently. The rats of each group were sacrificed in different process of diabetes, then urinary albumin excretion (UAE), urinary β2－MG excretion, plasma cholesterol, quantity of the expression of nephrin gene were measured. Results: The UAE and urinary β2－MG excretion rates of DM no treated groups were higher than control group, and these two rates of all groups treated with Simvastatin or Losartan were much lower than 8