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目的:观察低分子量肝素(LMWH)对糖尿病(DM)大鼠肾组织Wilm’s tumor-1(WT-1)蛋白表达的影响,探讨其可能的肾保护作用机制。方法:将雄性SD大鼠分为对照组、糖尿病组、LMWH治疗组。于LMWH治疗后第6周末观察肾小球细胞数及细胞外基质(ECM)聚积;定量检测肾小球WT-1蛋白的表达。间接免疫荧光法检测尿沉渣足细胞WT-1蛋白,阳性即为尿液足细胞(UPC)。结果:糖尿病组UPC、24h尿蛋白(UTP)均较对照组及LMWH治疗组明显升高(P<0.01或P<0.05)。病理组织学上,糖尿病组肾小球细胞数及ECM/肾小球毛细血管襻面积较LMWH组增多(P<0.05或P<0.01))。DM组肾组织WT-1蛋白表达显著低于对照组和LMWH组(P<0.01),对照组和LMWH组无统计学意义,UPC与UTP呈正相关(r_s=0.46,P<0.05)。结论:LMWH可减轻DM大鼠UAER及UPC的排泄,抑制肾小球细胞数及ECM增殖,恢复肾组织WT-1表达而有肾保护作用。
Objective: To observe the effect of low molecular weight heparin (LMWH) on the expression of Wilm’s tumor-1 (WT-1) in diabetic rat kidney and to explore the possible mechanism of renal protection. Methods: Male SD rats were divided into control group, diabetes group and LMWH treatment group. Glomerular cell number and extracellular matrix (ECM) accumulation were observed at the 6th week after LMWH treatment. The expression of glomerular WT-1 protein was detected quantitatively. Urinary sediment podocyte WT-1 protein was detected by indirect immunofluorescence method. Positive was urinary podocyte (UPC). Results: UPC and UTP in diabetic group were significantly higher than those in control group and LMWH treatment group (P <0.01 or P <0.05). Histopathologically, the number of glomerular cells and the area of glomerular capillary loop in ECM / glomeruli were increased in DM group compared with LMWH group (P <0.05 or P <0.01). The expression of WT-1 protein in DM group was significantly lower than that in control group and LMWH group (P <0.01). There was no significant difference between control group and LMWH group. UPC was positively correlated with UTP (r_s = 0.46, P <0.05). Conclusion: LMWH can relieve the excretion of UAER and UPC in DM rats, inhibit the proliferation of glomerular cells and ECM, and restore the expression of WT-1 in renal tissue.