摘要
目的探讨舒洛地特对糖尿病大鼠肾脏的保护作用及其相关机制。方法将33只Sprague Dawley大鼠随机分为正常对照组、糖尿病组和舒洛地特组,每组11只。造模后12周终止实验处死大鼠,取血、尿和肾脏标本,测定尿量、体质量、肾脏质量/体质量、血糖、糖化血红蛋白;测定血液和肾脏组织的丙二醛(MDA)和超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱苷肽过氧化物酶(GSH-PX)的活性;通过电镜观察肾脏超微结构的变化。结果12周终止实验时糖尿病各组大鼠的尿量、肾脏质量/体质量、血糖、HbA1c、血清和肾脏组织的MDA水平均明显高于正常组,而体质量、血清和肾脏组织的SOD、CAT、GSH-PX活性明显低于正常组(P<0.05);舒洛地特组大鼠的血清和肾脏组织的MDA水平明显低于糖尿病组,而SOD、CAT、GSH-PX的活性高于糖尿病组(P<0.05)。电镜显示模型组大鼠肾基底膜增厚,厚薄不均,上皮细胞内线粒体空化,舒洛地特组大鼠的肾脏组织超微结构损伤明显减轻。结论舒洛地特有效降低糖尿病大鼠尿微量白蛋白含量、改善肾脏超微结构、防止基底膜增厚、保护肾小球滤过屏障,减轻糖尿病大鼠肾脏损害的进展,其机制可能与舒洛地特抑制糖尿病大鼠过氧化反应和提高抗氧化能力有关。
Objective To investigate the renal protective effects of sulodexide and its anti-oxidative stress mechanism in diabetic rats. Methods Thirty male SD rats were randomized into 3 equal groups, namely the control group, diabetic group, and sulodexide treatment group. Twelve weeks after establishment of rat diabetic models and administration of sulodexide, the rats were sacrificed for measurement of the urine volume, body mass, kidney mass/body weight ratio, plasma glucose, and glycosylated hemoglobin （HbA1c）. Malondialdehyde （MDA） levels and superoxide dismutase （SOD）, catalase （CAT）, and glutathione peroxidase （GSH-PX） activities in the renal tissue or serum were tested. Electron microscopy was performed to observe the pathological changes in the kidneys. Results The urine volume, renal mass/body mass ratio, serum glucose, HbA1C, and serum and renal MDA levels all significantly increased in the diabetic rats in comparison with the normal controls （P〈0.05）. But the body weight and activities of SOD, CAT, and GSH-PX in the renal tissue in the normal control group were significantly higher than those in the diabetic and sulodexide group. After 12 weeks of sulodexide treatment, SOD, CAT, and GSH-PX activities in the renal tissue of rats were significantly increased in comparison with those in the diabetic rats （P〈0.05）. Electron microscopy showed obvious irregular thickening of the glomerular capillary basement membrane in the diabetic group with vacuolization in the mitochondria in the epithelial cells, and such pathological changes were significantly alleviated in the sulodexide treatment group. Conclusion Sulodexide can effectively lower the urinary albumin excretion rate, improve the ultrastructural renal pathologies and prevent glomerular basement membrane thickening in diabetic rats, probably in association with the reduction of the MDA levels and enhancement of SOD, CAT, and GSH-PX activities.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2009年第4期778-780,784,共4页
Journal of Southern Medical University
