白芍总苷对糖尿病大鼠肾小管-间质损伤的保护作用及机制

Protective action of total glucosides of paeony on renal tubulointerstitium and its mechanism in diabetic rats

目的探讨白芍总苷(TGP)对糖尿病大鼠肾小管-间质损伤的保护作用及机制。方法采用链脲佐菌素(STZ)诱导大鼠糖尿病模型。SD大鼠随机分对照组、模型组、白芍总苷给药组(50、100、200mg·kg-1·d-1口服),8wk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小管-间质骨桥蛋白(OPN);α-平滑肌肌动蛋白(α-SMA)表达,Western blot方法检测肾组织硝基酪氨酸(NT)表达。结果模型组大鼠TII明显高于对照组(P<0·01),TGP100、200mg·kg-1给药组TII明显低于模型组(P<0·05,P<0·01)。模型组肾小管-间质OPN与α-SMA蛋白表达明显高于对照组(P<0·01),TGP100、200mg·kg-1给药组肾小管-间质OPN表达明显低于模型组(P<0·01),TGP各剂量给药组肾小管-间质α-SMA蛋白均明显低于模型组(P<0·01)。模型组肾组织NT蛋白表达较对照组增加3·4倍,TGP50、100、200mg·kg-1给药8wk可使肾组织NT蛋白表达分别下降41·2%、43·8%与57·5%。结论白芍总苷对糖尿病大鼠肾小管-间质损伤有明显保护作用,其机制可能与抑制糖尿病肾小管-间质过高OPN与α-SMA表达有关。

Aim To study the protective action of total glucosides of paeony （TGP） on renal tubulointerstitium and its mechanism in diabetic rats. Methods Diabetes was induced by injection of streptozotocin in rats. Rats was randomly divided into three groups： control group, model group, model group treated with TGP. TGP （50, 100, 200 mg· kg^-1· d^-1） was orally administered once a day for 8 wk. Tubulointerstitial morphological analysis was performed in PAS stained section. Expressions of osteopontin （OPN） and α-smooth muscle actin （α-SMA） in renal tubulointerstitium were determined by immunohistochemistry method, expression of nitrotyrosine （NT） was measured by Western blot analysis. Results Increased indices for tubulointerstitial injury were significantly ameliorated by TGP treatment with 100 and 200 mg· kg^-1 in diabetic rats （P 〈0.05, 0. 01 ）. Elevated expression of OPN protein in renal tu-bulointerstitium in diabetic rats was only significantly inhibited by TGP treatment with 100 and 200 mg ·kg^-1（P 〈0. 01 ）, and increased expression of α-SMA protein was significantly inhibited by TGP treatment with 50, 100 and 200 mg· kg^-1 （ P 〈0. 01 ）. Western blot analysis noted that the expression of NT protein was increased 3.4 fold in the kidney in diabetic rats, TGP treatment with 50, 100 and 200 mg· kg^-1 could reduced the increased expression of NT protein by 41.2% ,43.8% and 57.5%. Conclusions TGP can prevent renal tubulointerstitium injury in diabetic rats, whose mechanism may be at least partly correlated with suppression on increased expression of OPN and α- SMA.