舒洛地特对糖尿病大鼠肾脏结构及功能的影响

Effect of sulodexide on structure and function of renal tissue in diabetic rats

目的探讨舒洛地特对链脲佐菌素(STZ)诱导的糖尿病大鼠尿白蛋白排泄率(UAER)及肾脏结构的影响。方法33只雄性SD大鼠随机分成正常对照组、糖尿病组及舒洛地特组,每组11只。糖尿病组和舒洛地特组在空腹10h后按65mg/kg一次性腹腔内注射STZ溶液,正常对照组注射等量生理盐水,72h后尾静脉血糖≥16.7mmol/L及尿糖≥卅且持续3d为造模成功。其中,糖尿病组成模9只,舒洛地特组成模10只。造模成功后,舒洛地特组给予10mg/(kg·d)舒洛地特灌胃,糖尿病组和正常对照组给予等量的生理盐水灌胃,疗程12周。用药结束后次晨测24h UAER,并在光镜、电镜下观察各组大鼠肾脏组织结构的病理变化。结果糖尿病组的24h UAER明显高于正常对照组,舒洛地特组24h UAER高于对照组,但明显低于糖尿病组,差异有统计学意义(P<0.05)。与对照组相比,在光镜和电镜下,糖尿病组大鼠肾脏组织表现出明显的病理结构改变,舒洛地特组肾脏病理改变则明显减轻。结论舒洛地特可降低糖尿病大鼠UAER,明显减轻糖尿病大鼠的肾脏病理损害,从而起到肾脏保护作用。

Objective To investigate the effects of sulodixide on the diabetic rats induced by streptozotocin （STZ） by observing the structural changes in renal tissue and detecting 24h urinary albumin excretion rate （UAER）. Methods Thirty three male Sprague Dawley （SD） rats were randomly divided into three groups （11 each）： normal control group, diabetic group, and sulodexide group. STZ （65mg/ kg） was injected into the abdominal cavity of rats in diabetic group and sulodexide group, while same amount of saline was injected into the rats in normal control group after 10-hour fasting. Diabetic model rats were confirmed when fasting blood glucose （FBG） level was over 16. 7mmol/L, urine glucose over （＋＋＋） persisting for 3 days. Diabetic models were successfully reproduced in 9 rats in diabetic group and 10 rats in sulndexide group. After diabetes was established, rats in sulodexide group received intragastric administration of 10mg/（kg·d） of sulodexide, while the rats in both diabetic group and control group received intragastric normal saline in same amount for 12 weeks. Once the treatment ended, 24-hour urine samples were collected to determine the 24h UAER, and the pathological changes in renal tissue were observed with optical microscope and electron microscope. Results The 24h UAER was significantly higher in the rats in diabetes group than that in normal control group （P〈0. 001） ; the 24h UAER was significantly lower in the rats in sulodexide group than that in diabetes group, but was higher than that in normal control group （P〈0. 001）. Obvious pathological changes in the renal tissues were observed with optical and electron microscope in diabetes group in contrast to that in the normal control group, but these changes were much ameliorated in sulodexide group. Conclusion The results of present study suggest that sulodexide can protect the renal function by abating the injury to the renal tissues and greatly reduce UAER.