低分子肝素对糖尿病大鼠早期肾脏病变的防护作用

目的探讨低分子肝素对实验性糖尿病大鼠早期肾脏病变的防护作用及机制.方法将大鼠随机分为正常对照组、糖尿病组和低分子肝素治疗组,每组各30只大鼠.分别于1、2、4周测定肌酐清除率、尿白蛋白、肾重、体重、肾脏肥大指数、部分凝血酶时间(APTT)和抗Xa因子活性,观察肾脏组织病理变化并进行体视学分析.结果低分子肝素治疗组于实验期间体重高于糖尿病组,第2、4周肌酐清除率分别为4.01 ml/min±0.39 ml/min及2.20 ml/min±0.34 ml/min;第4周尿24 h白蛋白为9.6 μg±3.0 μg,明显低于糖尿病组(P<0.05).APTT于治疗第2、4周分别为20.88 s和21.01 s,较糖尿病组延长(P<0.01),肾组织病理较糖尿病组有所改善.而两组血糖无明显差异(P>0.05).低分子肝素治疗组的肾脏肥大指数于1、2、4周分别为0.67±0.06,0.69±0.06、0.73±0.07(×102),高于糖尿病组(P<0.05).肾小球平均面积和体积密度于第4周时略高于糖尿病组,但无统计学意义.结论低分子肝素对糖尿病大鼠早期肾脏病变有一定程度的防护作用,其机制可能与改善肾小球内血液动力学有关.

The protective effect of low molecular weight heparin on early nephropathy in diabetic rats

Objective To investigate the protective effect of low molecular heparin on early nephropathy in diabetic rats and to explore its possible mechanism. Methods The rats were randomly divided into following groups: normal control rats, streptozotocin (STZ, 65 mg/kg) induced diabetic rats and diabetic rats treated with low molecular weight heparin (Fraxiparine, Nadroparin calcium 205 AXaIU/kg). The activity of anti Xa factor and the activated partial thromboplastin time (APTT) in plasma were assayed, the renal function and profile of kidney hypertrophy were measured, and the renal tissue were observed by light microscopy after 1, 2, 4 weeks of the treatment respectively. Results Compared with the untreated diabetic group, except for higher kidney hypertrophy index, LMWH treated diabetic rats presented less urinary albumin excretion, lower creatinine clearance rate (Ccr) and longer APTT than diabetic group without any treatment. Meanwhile, renal pathologic changes in LMWH treated group were improved. Conclusion Low molecular weight heparin possesses a renal protective effect on early diabetic nephropathy and its possible mechanism may be associated with the beneficial effect of LMWH on regulating abnormal diabetic renal hemodynamics.