Chen Shan, Fang Zhan, Zhu Zhonghua, Deng Anguo, Liu Jianshe, Zhang Chun
Department of Nephrology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2009 Dec;29(6):715-9. doi: 10.1007/s11596-009-0608-0. Epub 2009 Dec 29.
This study examined the effect of sulodexide on podocyte injury in rats with adriamycin nephropathy (AN). A total of 36 healthy male SD rats were randomly assigned to three groups: control group, AN group and sulodexide treatment group. Rat models of AN were established by a single tail intravenous injection of adriamycin (6.5 mg/kg) in both AN group and sulodexide treatment group. Sulodexide (10 mg/kg) was administered the rats in the treatment group once daily by garage from the first day of model establishment until the 14th day or the 28th day. Samples of 24-h urine and renal cortex tissues were harvested at day 14, 28 after the model establishment. Excretion of 24-h urinary protein was measured by Coomassie brilliant blue method. The pathological changes in renal tissues were observed by light microscopy and electron microscopy respectively. Heparanase mRNA was detected by RT-PCR. Expressions of desmin, CD2AP and heparanase were determined by immunohistological staining. The results showed that the expressions of heparanase mRNA and protein were increased in the glomeruli of AN rats at day 14 and 28 after the model establishment, which was accompanied by the increased expression of desmin and CD2AP. The mRNA and protein expression of heparanase was decreased in the sulodexide-treated rats as compared with AN rats at day 14 and 28. And, the protein expression of desmin and CD2AP was reduced as with heparanase in the sulodexide- treated rats. Proteinuria and podocyte foot process effacement were alleviated in the AN rats after sulodexide treatment. There was a positive correlation between the expression of heparanase and the expression of desmin and CD2AP (as well as 24-h urinary protein excretion). It was concluded that increased heparanase is involved in podocyte injury. Sulodexide can maintain and restore podocyte morphology by inhibiting the expression of heparanase in AN.
本研究探讨舒洛地昔对阿霉素肾病(AN)大鼠足细胞损伤的影响。将36只健康雄性SD大鼠随机分为三组:对照组、AN组和舒洛地昔治疗组。AN组和舒洛地昔治疗组均通过单次尾静脉注射阿霉素(6.5 mg/kg)建立AN大鼠模型。从模型建立第一天起至第14天或第28天,治疗组大鼠每天经灌胃给予舒洛地昔(10 mg/kg)。在模型建立后第14天、28天采集24小时尿液和肾皮质组织样本。采用考马斯亮蓝法测定24小时尿蛋白排泄量。分别通过光学显微镜和电子显微镜观察肾组织的病理变化。采用RT-PCR检测乙酰肝素酶mRNA。通过免疫组织化学染色测定结蛋白、CD2相关蛋白(CD2AP)和乙酰肝素酶的表达。结果显示,模型建立后第14天和28天,AN大鼠肾小球中乙酰肝素酶mRNA和蛋白表达增加,同时伴有结蛋白和CD2AP表达增加。与AN大鼠相比,舒洛地昔治疗组大鼠在第14天和28天时乙酰肝素酶的mRNA和蛋白表达降低。并且,舒洛地昔治疗组大鼠中结蛋白和CD2AP的蛋白表达与乙酰肝素酶一样降低。舒洛地昔治疗后,AN大鼠的蛋白尿和足细胞足突消失得到缓解。乙酰肝素酶的表达与结蛋白和CD2AP的表达(以及24小时尿蛋白排泄量)呈正相关。结论是乙酰肝素酶表达增加参与足细胞损伤。舒洛地昔可通过抑制AN中乙酰肝素酶的表达来维持和恢复足细胞形态。