低分子肝素对糖尿病大鼠肾脏病变的影响.docVIP

低分子肝素对糖尿病大鼠肾脏病变的影响 低分子肝素对糖尿病大鼠肾脏病变的影响 2010-02-23 刘元涛　袁申元　朱良湘　张京秀 　　【摘要】　目的　研究低分子肝素对糖尿病大鼠肾脏病变的保护作用及其机制。方法　观察低分子肝素对肾小球功能、形态及肾小球基底膜超微结构的影响。结果　(1)在病程不同时期(4、8、12、16周)治疗组尿白蛋白明显低于非治疗组(P＜0.05)；(2)16周时，光镜及电镜下治疗组肾小球系膜增生、基底膜增厚和足突融合等病变较非治疗组明显减轻，而两组血糖、肾小球平均截面积、肾小球平均体积、肾小球滤过率及血压无明显差异(P＞0.05)。结论　低分子肝素对糖尿病大鼠的肾脏病变具有一定防治作用，其机制可能不是通过改善血糖及血液动力学实现的。 　　【关键词】　肝素，低分子　　实验性　　糖尿病　　肾病 Effect of low molecular weight heparin on nephropathy in diabetic rats　　Liu Yuantao,Yuan Shenyuan,Zhu Liangxiang,et al.Department of Diabetes and Microcirculation,Tong Ren Hospital,affiliated to Capital University of Medical Sciences,Beijing,100005 　　【Abstract】　Objective　To evaluate the protective effect of low molecular weight heparin (LMWH) on diabetic nephropathy in streptozotocin-induced diabetic rats and to explore　　its　　possible　　mechanism. Methods Changes relating to glomerular function, structure and glomerular basement membrane ultrastructure were observed. Results　(1)At 4,8,12 and 16 weeks, the excretion of urine albumin of LMWH-treated group was lower than that of non-treated group (P＜0.05); (2)At the end of the experiment, the mesangial expansion and basement membrane thickening were obviously retarded in LMWH-treated group. But there was no difference in blood glucose level, mean glomerular area, mean glomerular volume, glomerular filtration rate and blood pressure between these two groups (P＞0.05). Conclusion　Low molecular weight heparin has a favorable effect on functional and morphological renal abnormalities in diabetic rats, which may not be achieved by changing glucose metabolism or improving renal haemodynamics. 　　【Key words】　Low molecular weight, heparin　　Experimental　　Diabetes mellitus　　Nephropathy (Chin J Endocrinol Metab, 1998, 14:257～259) 　　硫酸乙酰肝素(Heparan Sulfate, HS)是肾小球上皮细胞及内皮细胞产生的细胞外基质之一，是维持肾小球基底膜结构、功能的重要成分，HS分布于肾小球各种固有细胞的表面，参与肾小球细胞与细胞外基质之间相互作用的调节。糖尿病状态下肾小球基底膜HS的减少与糖尿病肾病(DN)的发生有关〔1〕。肝素是临床常用的抗凝药物之一，其化学结构与HS极为相似，体外实验表明肝素及其分解产物-低分子肝素可促进肾小球内皮细胞及系膜细胞HS合成〔2〕，并明显降低糖尿病患者尿蛋白排除率〔3〕。目前肝素