【Objective】To investigate the effect of TGP on activation of JAK/STAT signal transduction in the kidney from diabetic rat and explore the possible renoprotection mechanisms. 【Methods】Diabetes was induced with streptozotocin in rats, and TGP was orally administered once a day for 8 weeks to rats. The expression of the p- JAK2, p-STAT3 and 1α (IV) collagen protein were determined by western blot analysis and expression of TGF-β1 was measured by immunohistochemistry in the kidney. 【Results】Elevated 24 hours urinary albumin excretion rate was markedly attenuated by TGP treatment. Western blot analysis and immunohistochemistry noted that the expression of p-JAK2, p-STAT3, 1α (IV) collagen protein and TGF-β1 protein in the kidney were significantly increased in diabetic rats, while they were significantly inhibited by TGP treatment. 【Conclusion】Our data suggest that TGP treatment ameliorates early renal injury via the inhibition of activation of JAK/STAT signal transduction and the relevant TGF-β1-collagen IV expression in the kidney from diabetic rat.

目的探讨白芍总苷（TGP）对糖尿病肾病的治疗作用及其可能的作用机制。方法采用链佐星（STZ）诱导大鼠糖尿病模型。大鼠随机分为对照组、糖尿病模型组、TGP组（50,100和200mg.kg-1,ig,每天1次,共8周）。8周后检测肾组织总抗氧化能力（T-AOC）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-PX）活性,应用Western蛋白印迹法检测肾组织硝基酪氨酸（NT）蛋白的表达,免疫组化方法检测肾组织转化生长因子β1（TGFβ1）蛋白的表达。结果与对照组相比,模型组肾组织T-AOC,SOD和CAT活性明显降低;TGP200mg.kg-1给药组T-AOC,SOD和CAT活性明显高于模型组。模型组肾组织NT蛋白表达较对照组增加3.4倍,给予TGP50,100和200mg.kg-18周可分别使肾组织NT蛋白表达下降41.2%,43.8%和57.5%。模型组肾组织TGFβ1蛋白表达明显高于对照组,TGP50,100和200mg.kg-1组TGFβ1蛋白表达明显低于模型组。结论糖尿病大鼠肾脏存在氧化应激反应,TGP抗糖尿病肾病的作用可能与其抗氧化活性有关。

Aim To investigate the effect of mycophenolate mofetil(MMF)on the expression of Nephrin and Podocin and its mechanism in the kidney of diabetic rats.Methods Diabetes was induced with streptozotocin after uninephrectomy,and MMF(10 mg·kg-1·d-1 was orally administered once a day for 8 wk.Blood glucose and 24 hours urinary albumin excretion rate(AER)were measured.The expression of ED-1,Nephrin,Podocin,interleukin-1(IL-1)and tumor necrosis factor-α(TNF-α)protein in the kidney were determined by immunohistochemistry or Western blot analysis.Results Elevated AER was markedly attenuated by MMF treatment(P0.05).ED-1-positive cells were significantly increased in glomeruli of diabetic rats,which was effectively suppressed by MMF treatment(P0.05).Western blot analysis showed that the expression of Nephrin and Podocin protein was reduced in the kidney of diabetic rats,and MMF treatment significantly increased the expression of Nephrin and Podocin protein(P0.01).The expression of IL-1 and TNF-α protein in the kidney was significantly increased in diabetic rats,which was significantly inhibited by MMF treatment(P0.01).Conclusions MMF could decrease AER in diabetic rats,whose mechanism may be at least partly correlated with upregulating the expression of Nephrin and Podocin in the kidney.

Aim To investigate the effect of total glucosides of paeony (TGP) on the expression of intercellular adhesion molecule-1 (ICMA-1) and transforming growth factor 1 (TGF 1) protein in the kidney in experimental diabetes. Methods Diabetes was induced with streptozotocin in Sprague-Dawley rats. TGP (50, 100, 200 mg·kg-1·d-1) was orally administered once a day for 8 wk to rats. Results Elevated urinary albumin excretion rate (AER) was markedly attenuated by TGP treatment with 50, 100 and 200 mg·kg-1. Increased malondialdehyde (MDA) level was only significantly reduced by TGP treatment with 200 mg·kg-1. Elevated glomerular volume was significantly attenuated by TGP treatment with 50, 100 and 200 mg·kg-1, and increased indices for tubulointerstitial injury were only ameliorated by TGP treatment with 100 and 200 mg·kg-1. Western blot analysis noted that the expression of 1 type Ⅳ collagen protein was increased 2.7 -fold in the kidney in diabetic rats, TGP treatment with 50, 100 and 200 mg·kg-1 could reduced increased expression of 1 type Ⅳ collagen protein by 47.9 %, 60.4 % and 72.9 %. The expression of ICAM-1 and TGF 1 protein in the kidney were significantly increased in diabetic rats, which were all significantly inhibited by TGP treatment. Conclusion Our data suggest that TGP treatment ameliorates early renal injury via the inhibition of oxidative stress and overexpression of ICAM-1 and TGF-1 in renal tissue in diabetic rats.