白芍总苷对糖尿病大鼠肾小管-间质细胞转分化的影响

目的探讨白芍总苷（TGP）对糖尿病大鼠肾小管-间质细胞转分化的影响。方法建立链脲佐菌素（STZ）诱导的大鼠糖尿病模型，将大鼠随机分对照组、模型组、TGP给药组（50、100、200mg·kg-1·d-1灌胃），8w后观察肾小管-间质损伤指数（TII）的变化，应用免疫组化方法检测肾组织E-钙黏蛋白（E-cadherin，E-cad）、α平滑肌肌动蛋白（a-smooth muscleactin，α-SMA）以及波形蛋白（Vim—entin，Vh）的表达。结果TGP给药呈剂量依赖性降低糖尿病大鼠24h尿白蛋白排泄率。模型组TⅡ明显高于对照组，TGP给药组（100mg·kg-1·d-1与200mg·kg-1·d-1）TII明显低于模型组。模型组肾小管-间质E-cad表达明显低于对照组（P〈0．05），TGP50、100、200mg·kg-1·d-1给药组E-cad表达明显高于模型组（P〈0．01）。模型组肾小管-间质α—SMA与Vim蛋白表达明显高于对照组（P〈0．叭），TGP50、100、200mg·kg-1·d-1给药组肾小管-间质α-SMA与Vim蛋白表达明显低于模型组（P〈0．01）。结论TGP可降低肾小管-间质α—SMA和vim的表达，增加E—cad的表达，抑制肾小管-间质细胞转分化。

Effects of total glucosides of paeony on transdifferentiation of renal tubulointerstitial cells in diabetic rats

Objective To investigate the effect of total glucosides of paeony （TGP） on transdifferen- tiation of renal tubulointerstitial cells in diabetic rats. Methods Diabetes was induced by injection of strepto- zotocin in rats. Rats were randomly divided into three groups： control group, model group, TGP group. TGP （50, 100,200 mg·kg-1·d-1 ） was orally administered once a day for 8 weeks. Tubulointerstitial mor- phological changes were observed in PAS-stained sections. The expression of E-cadherin （E-cad）, a-smooth muscle actin （α-SMA） and vimentin （Vim） in renal tubulointerstitium was detected by using immunohisto- chemistry. Results Elevated 24-h urinary albumin excretion rate was markedly attenuated by TGP treatment with 50, 100 and 200 mg.·kg-1·d-1 in diabetic rats. Increased indices for tubulointerstitial injury were sig- nificantly ameliorated by TGP treatment with 100 and 200 mg·kg-1·d-1 in diabetic rats （P〈0.05, 0. 01 ）. In renal tubulointerstitium in diabetic rats, decreased expression of E-cad protein was significantly inhibited by TGP treatment with 50, 100 and 200 mg·kg-1·d-1（P〈0. 01） and elevated expression ofα-SMA and Vim protein was also significantly inhibited by TGP treatment with 50, 100 and 200mg·kg-1·d-1（P〈 0. 01 ）. Conclusions TGP can down-regulate the expression of a-SMA and Vim, and up-regulate the expres- sion of E-cad in diabetic renal tubulointerstitial cells and restrain the process of tubulointerstitial cells trans- differentiation in diabetic rats.