2型糖尿病肾病大鼠肾小管间质中的中期因子及肝细胞生长因子的表达

The Expression of Midkine and HGF of Tubular-Interstitial in Rat Model of Type 2 Diabetic Nephropathy

目的:探讨2型糖尿病肾病(T2DN)大鼠肾小管间质的病理变化,观察中期因子(MK)和肝细胞生长因子(HGF)表达变化及其相互关系。方法:60只SD大鼠随机均分为对照组和造模组。采用单侧肾切除+高糖高脂+链脲左菌素(STZ)复制T2DN模型。6周和12周时测定24h尿微量白蛋白(24hUMA)、空腹血糖(FBG)、计算肾质量与体质量的比值(KW/BW)。HE染色及PASM染色法观察肾小管间质的病理变化;免疫组化法检测肾小管间质中MK和HGF的表达。结果:与对照组比较,造模组大鼠FBG、KW/BW及24hUMA明显升高(均P<0.01);造模组6周及12周MK和HGF的表达高于对照组(均P<0.01);造模组MK12周的表达高于6周(P<0.05),HGF12周的表达低于6周(P<0.01)。相关分析显示MK与HGF的表达在12周时呈负相关(r=-0.525,P<0.01)。结论:MK和HGF在DN肾小管间质中表达发生变化,提示两者可能共同参与了DN的发病。

Objective：To investigate the changes of tubular-interstitial pathomorphology and the expression of midkine（MK） and hepatocyte growth factor（HGF） in the rat model of type 2 diabetic nephropathy（T2DN）,and the relationships between MK and HGF thereof.Methods：Sixty male SD rats were randomly divided into two groups：control group and model group.T2DN model was established by high-glucose and high-fat diet and intraperitoneal streptozotocin（STZ） after unilateral nephritic excision.The 24-hour urine protein（24 hUMA） and fasting blood glucose（FBG） were detected at 6-week and 12-week.The ratio of kidney weigh to body weigh（KW/BW）was calculated.The tubular-interstitial pathomorphological changes were detected with HE and periodic acid-silver methenamine（PASM） staining.The expressions of MK and HGF in tubular-interstitial were determined by immunohistochemistry.Results：The levels of FBG,KW/BW and 24 hUMA were obviously increased in the model group compared with those of control group（P 0.01）.At 6-week and 12-week,the expression levels of MK and HGF were significantly higher in rats of model group compared with those of control group（P 0.01）.And the expression of MK was obviously increased at 12-week than that in 6-week in rats of model group（P 0.05）.But the expression of HGF was obviously decreased in 12-week than that of 6-week of model group（P 0.01）.At 12-week of model group,there was a negative correlation between expression levels of MK and HGF（r =-0.525,P 0.01）.Conclusion：The changes of MK and HGF in different stages of tubular-interstitium of diabetic nephropathy can partly explain the pathogenesis of diabetic nephropathy.