摘要
目的研究血管紧张素1-7（Angl-7）对糖尿病大鼠肾小管间质纤维化的影响及其可能机制。方法32只雄性Wistar大鼠被随机分为4组：健康对照组（NC组）、模型组（DM组）、替米沙坦组（TM组）、治疗组（T组）。建模成功后第9周末检测各组大鼠24h尿蛋白量、尿NAG／Cr、血糖、血胰岛素、三酰甘油（TG）、总胆固醇（TC）、BUN、Scr、血K^＋及血Na^＋；PAS染色观察肾脏病理改变；实时定量PCR法检测各组大鼠肾脏组织中转化生长因子B1（TGF-β1）、过氧化物酶体增殖物激活受体（PPAR）叫、d平滑肌肌动蛋白（α-SMA）mRNA水平；Western印迹法检测PPARγ、α-SMA、TGF．Bl蛋白表达。结果（1）第9周末，DM组大鼠血压、尿蛋白量、肾质群质量较NC组显著升高（P〈0．05），TM组及T组较DM组显著降低（P〈0．05），且T组变化更明显。（2）DM组第9周末肾间质损伤指数显著高于NC组（P〈0．05），TM组及T组则低于DM组（P〈0．05）。（3）实时定量PCR结果显示，DM组TGF-β1、d—SMAmRNA水平显著升高（P〈0．05），PPAR^ymRNA水平显著下降（P〈O．05），TM组及T组较DM组TGF-β1、仪．SMAmRNA水平均显著下降（P〈0．05），PPARγ mRNA水平显著上升（P〈0．05），且T组变化更明显。（4）Western印迹结果显示，DM组TGF-β1、α-SMA蛋白水平显著升高（P〈0．05），PPAR~蛋白水平显著下降（P〈0．05），TM组及T组较DM组TGF．B1、α-SMA蛋白水平均显著下降（P〈0．05），PPAR~／蛋白水平显著上升（P〈O．05），且T组变化更明显。结论Angl．7在体内可通过上调PPARγ表达，抑制α-SMA表达，对糖尿病大鼠肾小管问质纤维化可能具有抑制作用。
Objective To investigate the effects of angiotensinl-7 （Angl-7） on renal tubulointerstitial fibrosis of diabetic rats. Methods Thirty-two male Wistar rats were randomly divided into four groups： normal control group, diabetic group, tclmisartan group, Angl-7-treated group. For 9 weeks after diabetes mellitus model established, 24 h proteinuria, urine NAG/Cr, glucose, insulin, TG, TC, BUN, Scr, Na~ and K＋ were assessed. Renal pathological changes were evaluated by PAS staining; Expression of TGF-β1, PPARγ and ct-SMA mRNA was detected by real-time PCR; Protein levels of PPARγ, ot-SMA and TGF-β1 were detected by Western blotting. Results （1）At the end of the ninth week, the blood pressure, proteinuria, renal weight/body weight in group DM were significantly higher than those in group NC （P〈0.05）. （2）Renal interstitialfibrosis in group DM was obviously severe as compared to group NC （P〈O.05）, but was improved in group TM and group T（P〈O.05）. （3）TGF-β1 and α-SMA mRNA in group DM were significantly increased, and PPARγ/ mRNA was significandy decreased. Compared with group DM, TGF-β1 and α-SMA mRNA were significantly decreased, and PPARγ mRNA was significantly increased in group TM and group T, especially in group T. （4）TGF-β1 and α-SMA in group DM were significantly increased, and PPARγ/ decreased significantly. Compared with group DM, TGF-β1 and α-SMA decreased significantly, PPARγ/ increased significantly in group TM and group T, especially in group T. Conclusion Angl-7 inhibits high glucose-induced α-SMA expression in vivo through up-regulating the PPAR expression and may inhibit renal tubulointerstitial fibrosis of diabetic rats.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2012年第10期798-803,共6页
Chinese Journal of Nephrology
基金
国家自然科学基金（81070566）
