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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 4.0 1ml/min± 0 .39ml/min及 2 .2 0ml/min± 0 .34ml/min ;第 4周尿 2 4h白蛋白为 9.6 μg± 3.0 μg,明显低于糖尿病组(P <0 .0 5 )。APTT于治疗第 2、4周分别为 2 0 .88s和 2 1.0 1s,较糖尿病组延长 (P <0 .0 1) ,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 .0 5 )。低分子肝素治疗组的肾脏肥大指数于 1、2、4周分别为 0 .6 7± 0 .0 6 ,0 .6 9± 0 .0 6、0 .73± 0 .0 7(× 10 2 ) ,高于糖尿病组 (P <0 .0 5 )。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
Objective To investigate the protective effect and mechanism of low molecular weight heparin on early diabetic nephropathy in experimental diabetic rats. Methods The rats were randomly divided into normal control group, diabetic group and low molecular weight heparin treatment group, each group of 30 rats. Creatinine clearance, urinary albumin, kidney weight, body weight, renal hypertrophy index, partial thrombin time (APTT) and anti-factor Xa activity were measured at 1, 2, and 4 weeks respectively. Pathological changes of renal tissues were observed and analyzed by stereological methods . Results The low molecular weight heparin group had higher body weight than the diabetic group during the experimental period. The creatinine clearance rates at the second and fourth week were 4.01 ml / min ± 0.39 ml / min and 2.020 ml / min ± 0.34 ml / min, respectively. 4 weeks urinary albumin 24 h was 9.6 μg ± 3.0 μg, significantly lower than the diabetic group (P <0.05). APTT in the first and second week of treatment were 20.88s and 2.01s, respectively, which were longer than those in the diabetic group (P <0.01). The pathological changes of renal tissue in diabetic group were improved. There was no significant difference between the two groups (P> 0.05). In the low molecular weight heparin group, the renal hypertrophy index at 1, 2 and 4 weeks were respectively 0.67 ± 0.60, 0.96 ± 0.60, 0.73 ± 0.07 (× 10 2 ), Higher than diabetic group (P <0.05). Glomerular average area and bulk density in the 4th week slightly higher than the diabetic group, but not statistically significant. Conclusion Low molecular weight heparin can protect diabetic nephropathy from diabetic nephropathy to a certain extent, and its mechanism may be related to the improvement of hemodynamics in glomeruli