LY333531下调大鼠糖尿病模型肾组织结缔组织生长因子表达

目的　探讨LY333531对大鼠糖尿病模型肾组织结缔组织生长因子(CTGF)表达的影响。方法　建立链脲佐菌素(STZ)诱导糖尿病模型,随机分对照组,糖尿病组及LY333531给药组 ( 10mg/(kg·d),灌胃。8周后观察各组体重、肾重、肾重 /体重、24h尿白蛋白排泄率 (AER)及肾组织蛋白激酶C(PKC)活性的变化,行PAS染色肾小球病理形态学观察及CTGF免疫组化。结果　LY333531给药组大鼠体重明显高于模型组 (P<0 05),肾重、肾重 /体重、AER及肾小球面积(AG)、肾小球容量 (VG)及系膜区面积 (AM)明显低于糖尿病组(P<0 05,P<0 01);模型组肾组织PKCt活性、PKCc活性、PKCm活性及PKCm/PKCc明显高于对照组(P<0 05, P<0 01);LY333531给药组PKCt活性、PKCc活性、PKCm活性及PKCm/PKCc明显低于模型组 (P<0 05)。模型组肾小球CTGF表达明显高于对照组 (P<0 01),LY333531对其有明显抑制作用 (P<0 05 )。结论　LY333531对糖尿病肾脏有明显保护作用,机制可能与抑制肾组织CTGF过度表达有关。

LY333531 down-regulates the expression of connective tissue growth factor in the kidney of diabetic rats

Objective To investigate the effect of LY333531 on the expression of connective tissue growth factor (CTGF) the kidney of diabetic rats. Methods Diabetes was induced by injection of streptozotocin (STZ). Rats were randomly divided into three groups: control group, model group, LY333531(10 mg/kg/d) treatment group. 24 hours urinary albumin excretion rate (AER) and activity of protein kinase C (PKC) were determined after 8 weeks. Glomerular morphology was observed by light microscopy, and CTGF immunohistochemistry was performed in glomeruli. Results Increased kidney weight (KW), KW/body weight (KW/BW), AER and glomerular area, glomerular volume as well as mesangial area were significantly attenuated by treatment with LY333531( P <0 05). PKC activities in renal tissue were significantly lower in the LY333531 group compared with the model group ( P <0 05). Compared with the control, glomerular expression of CTGF was significantly increased in the model group ( P <0 01), which was significantly inhibited by LY333531 ( P <0 05). Conclusion Mechanism of renoprotection of LY333531 may be, at least partly, correlated with suppression on overexpression of CTGF in renal tissue in diabetic rats.