舒洛地特对糖尿病肾病大鼠肾脏乙酰肝素酶及碱性成纤维细胞生长因子表达影响

Effect of sulodexide on expression of heparanase and basic fibroblast growth factor in rats with diabetic nephropathy

目的:探讨舒洛地特对糖尿病肾病(diabetic nephropathy,DN)大鼠肾组织乙酰肝素酶(heparanase,HPA)、碱性成纤维细胞生长因子(basic fibroblast growth factor,b-FGF)表达的影响。方法:70只雄性SD大鼠随机分为对照组、模型组、DN舒洛地特治疗组(治疗组)。模型组和治疗组腹腔注射链脲佐菌素60 mg/kg建立DN模型,治疗组腹腔注射舒洛地特10 mg/(kg.d),对照组、模型组腹腔注射等剂量生理盐水共8周。分别于第4,8周末,留尿测定大鼠24 h尿蛋白定量,并将其处死,留取肾脏采用逆转录聚合酶联反应及免疫组织化学技术检测大鼠肾组织HPA、b-FGF的表达。结果:第4,8周末,模型组24 h尿蛋白定量、肾脏组织HPA mRNA、蛋白HPA、b-FGF的表达较对照组和治疗组明显升高(P<0.01)。结论:舒洛地特可抑制DN肾脏HPA和b-FGF的表达,降低蛋白尿,延缓肾小球硬化。

Objective To study the effect of sulodexide on the expression of heparanase and basic fibroblast growth factor in rats with diabetic nephropathy.Methods Seventy male SD rats were randomly divided into control group,diabetic nephropathy group and sulodexide group.Diabetic nephropathy group and sulodexide group received peritoneal injection of 60 mg/kg streptozotocin.Sulodexide group received peritoneal injection of 10 mg/（kg·d） of sulodexide for 8 weeks,while diabetic group and control group received intraperitoneal normal saline injection in the same dose for 8 weeks.The 24-hour proteinuria was measured in four and eight weeks.The rats were sacrificed.Immunohistochemistry and reverse transcription PCR techniques were used to detect the expression of heparanase and basic fibroblast growth factor in kidney in rats.Results Compared with normal control and sulodexide group,the 24-hour proteinuria,the expression of HPA mRNA,the protein of heparanase and basic fibroblast growth factor increased greatly in diabetic nephropathy group（P0.01） in four and eight weeks.Conclusion Sulodexide can reduce the proteinuria and lower the glomerulosclerosis by inhibiting the expressions of heparanase and basic fibroblast growth factor in diabetic nephropathy.