PKCβ抑制剂LY333531对大鼠糖尿病模型肾脏巨噬细胞浸润的影响

探讨PKCβ抑制剂LY3335 31对大鼠糖尿病模型肾组织巨噬细胞浸润的影响。建立STZ诱导的大鼠糖尿病模型 ,随机分对照组、模型组与LY3335 31给药组 ,每组 1 0只。 8周后检测 2 4h尿白蛋白排泄率 (AER )及肾组织PKC活性 ;PAS染色观察肾小球病理形态学指标 ;应用免疫组化方法检测肾组织ED 1及MCP 1、ICAM 1表达。结果 :(1 )模型组大鼠肾重、肾重/体重、AER及肾小球面积、肾小球容量、系膜区面积明显高于对照组 (P <0 0 5 ,P <0 0 1 ) ,LY3335 31给药组这些改变明显减轻 (P <0 0 5 ) ;(2 )LY3335 31给药组肾组织细胞膜、细胞浆PKC活性明显低于模型组 (P <0 0 5 ) ;(3)模型组肾小球ED 1阳性细胞数及MCP 1、ICAM 1表达明显高于对照组 ,LY3335 31给药组肾小球ED 1阳性细胞数及MCP 1、ICAM 1表达明显低于模型组 (P <0 0 5 )。表明LY3335 31对糖尿病大鼠肾脏有明显保护作用 ,其机制可能部分与抑制肾组织巨噬细胞浸润有关。

Effect of Protein Kinase Cβ Inhibitor LY333531 on Macrophage Recruitment in Kidney of Diabetic Rats

To investigate the effect of protein kinase C(PKC)β inhibitor LY333531 on macrophage recruitment in kidney of diabetic rats, diabetes was induced by injection of streptozotocin(STZ)after uninephrectomy. Rats were randomly divided into three groups:control, diabetes, diabetes treated with LY333531(10 mg/kg·d by gavage). 8 weeks after STZ injection, 24 hours albumin excretion rate(AER)were measured, and glomerular morphology were observed by light microscopy. The activity of PKC in renal tissue was determined. Immunohistochemistry for ED-1, MCP-1 and ICAM-1 were performed by streptavidin-biotin complex(SABC)technique. It was found that increased kidney weight(KW), ratio of KW to body weight(KW/BW), AER and glomerular area(A_G), glomerular volume(V_G)as well as mesangial area(A_M)on histological examination of the kidney were significantly attenuated by treatment with LY333531(P<0.05,P<0.01). Elevated PKC activity in renal tissue were also remitted by LY333531(P<0.05). Compared with control, glomerular macrophage recruitment and expression of MCP-1 and ICAM-1 were significantly increased in diabetic rats(P<0.01), which were all significantly inhibited by LY333531(P<0.05). It concludes that mechanism of renoprotection of LY333531 may be correlated, at least partly, with suppression on increased macrophage recruitment in diabetic renal tissue.