2型糖尿病肾病大鼠肾小管间质中中期因子及肝细胞生长因子的表达

目的：探讨2型糖尿病肾病(DN)大鼠肾小管间质的病理变化及中期因子（MK)、肝细胞生长因子(HGF)表达变化及其相互关系.方法：60只SD大鼠随机分为正常对照组（A组，24只）、糖尿病组（B组，36只）。采用单侧肾切除+高糖高脂+STZ复制T2DN模型。6周和12周时收集各组大鼠24小时尿测定24小时尿微量白蛋白，取血测空腹血糖，并计算肾重与体重的比值;用HE染色及PASM染色方法观察肾小管及间质的病理变化;用免疫组化法检测肾小管间质中MK和HGF的表达变化，并进行半定量分析。结果：（1）与正常对照组比较，糖尿病组大鼠空腹血糖（FBG）、肾重与体重的比值(KW/BW)及尿微量白蛋白均明显升高(p<0.05)。（2）糖尿病组大鼠部分肾小管上皮细胞出现萎缩、脱落、空泡化,基底膜增厚及小管间质纤维化。（3）免疫组织化学方法提示糖尿病组MK和HGF在6周及12周末的表达均高于正常对照组(p<0.01)；MK在12周末的表达高于6周末，有显著性差异(p<0.05)；HGF在12周末的表达低于6周末，差异有统计学意义(p<0.05).(4) 在糖尿病组，相关分析显示MK与HGF的表达成负相关（r=-0.525，P<0.01）。结论：MK和HGF在早期DN的肾小管间质中表达发生变化,提示两者可能共同参与了糖尿病肾病的发病。

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

Objective: To observe the expression of midkine and HGF in the renal tubles of diabetic rats and to investigate their relationships .Methods:sixty male Sprague-Dawlry rats were randomly divided into two groups:normal control group(n=24)and diabetes mellitus group(n=36).Type 2 diabetic nephropathy were induced by high-glucose and high-fat diet and intraperitonesl STZ after unilateral nephritic excision. At the end of 6th week and the 12th week after diabetes mellitus model established,blood glucose and 24 hours urine protein were determined,and body weight were weighed,and then rats were killed to collect the serum and kidney.We calculated the ratio of kidney weigh to body weigh(KW/BW). The tubular structural changes were examined with HE staining and periodic acid-silver methenamine staining at 6th week and the 12th week. The protein expression of midkine and HGF intubular-interstitial were determined by immunohistochemistry.Results:(1) FBG,KW/BW and 24 hours urine protein were obviously increased in the diabetes mellitus group compared with normal control group(P<0.05).(2) There were severe structural alterations of tubular-interstitium in diabetes mellitus group .(3) At the end of the 6th week, the12th week after diabetes mellitus model established,immunohistochemistry revealed a significant increase in the expression of MK and HGF in the kidney in diabetes mellitus group compared with normal control group(P<0.01). At the end of the 12th week , the expression of MK was obviously increased In diabetes mellitus group compared with the 6th week(P<0.05), the expression of HGF was obviously decreased In diabetes mellitus group compared with the 6th week(P<0.05).(4) In diabetes mellitus group,there were negative correlations between midkine and HGF(r=-0.525,P<0.01).Conclusion: The expression of midkine and HGF in tubular-interstitium are unbalanced,which possibly participated in pathogenesis of diabetic nephropathy.