国产低分子肝素对阿霉素肾病大鼠尿蛋白的影响

目的探讨国产低分子肝素海普宁是否具有降低大鼠阿霉素肾病蛋白尿,减轻足突细胞损害的作用。方法健康雄性SD大鼠尾静脉一次性注射阿霉素6.5mg/kg建立肾病模型,按给药方法分3组:对照组(5只):静脉注射生理盐水的同时,腹腔注射生理盐水,每日1次,按2mL/kg给予;肾病组(25只):静脉注射阿霉素的同时,腹腔注射生理盐水,每日1次,按2mL/kg给予;治疗组(25只):静脉注射阿霉素的同时,腹腔注射海普宁,每日1次,按200IU/kg给予(海普宁按100IU/mL溶解)。各组均于0d、3d、7d、14d、21d、28d收集24h尿液,对照组于第28天,肾病组及治疗组于收集尿液结束当天各取大鼠5只,留取肾组织及血液标本进行检测。结果与对照组相比,肾病组0d、3d尿蛋白无增加(P>0.05),从第7天开始增加(P<0.05),随时间延长逐渐增多,21d、28d达高峰,28d与21d相比,尿蛋白稍增加,但无统计学意义(P>0.05);治疗组尿蛋白演变过程与肾病组相似,亦第7天开始增加(P<0.05),第21天、28天达高峰,但与等天数肾病组相比,尿蛋白明显减少(P<0.05)。与对照组相比,肾病组血清ALB于第7天开始下降(P<0.05),第14d天达最低值,第21天、第28天较14d稍升高,但仍处低水平状态,无统计学差异(P>0.05);治疗组ALB下降过程与肾病组相近,但比同等天数肾病组及治疗组下降的少(P<0.05)。肾病组TG、ChoL第14天开始升高(P<0.05),第21天达高峰,第28天较21d下降(P<0.05);治疗组与同等天数肾病组相比增高较少(P<0.05)。光镜:肾病组:于第7天可见蛋白管型,14d较易见到蛋白管型,第21天、28天肾小球出现轻度系膜增生性改变,可见大量蛋白管型及间质纤维化;治疗组与肾病组相比,蛋白管型明显减少,无间质纤维化。电镜:肾病组:于第3天可见到足突融合,第14天最明显,第21天、28天出现足突细胞变形,体积变大,胞质中微丝增多,毛细血管袢闭塞、充血,大量红细胞填塞,内皮细胞孔消失,基底膜正常;与肾病组相比,治疗组足突细胞融合明显减轻,无毛细血管袢闭塞及足突细胞变形和体积增大。结论国产低分子肝素海普宁具有降低大鼠阿霉素肾病蛋白尿的作用,而且这种作用可能通过稳定足突细胞结构实现。

Effect of domestic low-molecular-weight heparin on proteinuria in adriamycin nephrosis rats

Objective To observe the effect of domestic low-molecular-weight heparin(LMWH)(Heparan)on proteinuria and podocyte injury in adriamycin nephrosis rats.Methods Animal models were made by giving a single tail-vein injection of adriamycin(6.5 mg/kg,to young male rats of Sprague-Dawley strain.Rats were divided into three groups:control group(CG),nephropathy group(NG)and treatment group(TG).Rats of nephropathy group received the tail-vein injection of adriamycin and abdominal injection of saline while the rats of treatment group received the abdominal injection of heparin,Rats of control group received the injection of saline both in tail-vein and abdomen.24 h urine was collected at 0 d,3 d,7 d,14 d,21 d,28 d of all the rats.Rats of CG were killed at the 28 th day while 5 rats of TG and NG were killed after each urine collection.Kidney tissue and blood sample were taken for the following research.Results Compared with the CG rats,no urine protein increase was observed at 0d,3d in NG rats(P>0.05).Urine protein volume began to increase from 7 d and reach the peak at 21 d and 28 d.TG rats showed the similar change at the urine protein volume while the same day urine protein volume decreased.Compared with the CG rats,serum ALB of NG rats began to decrease from the 7 d and reach the lowest point at 14 d.TG rats also showed the similar change at the serum ALB.Triglyceride and cholesterol concentration of NG rats elevated from the 14 d,reach the peak at 21 d.LM:NG:protein casts were observed at 7 d and were prone to be found at 14 d.Mild mesangial proliferation appeared at 21 d and 28 d,large amount of protein casts and intestinal fibrosis were found.Compared with the NG,protein casts of TG rats decreased significantly and no intestinal fibrosis was found.EM:NG:merge of foot process appeared at 3 d and was most notable at 14 d.At 21 d and 28 d deformation and enlargement of pococyte cell appeared and microfilament growed in number and there is no change in basemembrane.Fusion of foot processes relieved at TG rats,no presence of deformation and enlargement of podocyte cell was found.Conclusion Domestic low-molecular-weight,heparin decreased proteinuria in adriamycin nephrosis rats by stabilizing the architecture of podocyte.