TAFI在2型糖尿病肾病肾损伤发病机制中的作用

Role of Plasma TAFI in the Pathogenesis of Kidney Injury Induced by Type 2 Diabetes

目的:探讨血浆凝血酶激活的纤溶抑制物(TAFI)在2型糖尿病(T2DM)大鼠肾损伤发病机制中的作用。方法:选用雄性Wistar大鼠36只,随机分成3组(正常组、糖尿病假手术组、糖尿病手术组),每组12只。正常组予以普通饲料喂养并腹腔注射柠檬酸缓冲液;另外2组予以高糖高脂饲料喂养及腹腔注射链脲佐菌素(STZ),糖尿病手术组予以右肾切除术诱导T2DM肾病模型。检测3组血生化、凝血指标和尿蛋白,同时观察肾脏病变情况。结果:糖尿病手术组的体重、肾指数、血糖(FBG)、胰岛素(INS)、肌酐清除率(Ccr)、血脂、24 h尿蛋白、TAFI等水平明显高于另外2组,肾脏HE染色显示上皮细胞肿胀,水样变、空泡变性,肾小管扩张,肾小球基底膜增厚,系膜区增宽,细胞外基质增多。肾指数、损伤评分、肾小球面积及体积与另外2组相比,均有统计学意义。结论:三联法(高糖高脂饮食+单侧肾脏切除+小剂量链脉佐菌素STZ)能建立稳定的符合T2DM肾病大鼠模型;TAFI参与T2DM大鼠肾损伤发生发展。

Objective： To explore the role of plasma thrombin activated fibrinolysis inhibitor（ TAFI） in the pathogenesis of type 2 diabetic mellitus（ T2DM）-induced kidney injury in rats. Methods Thirty-six one-month-old Wistar rats were randomly divided into three groups（ normal diet group,T2 DM sham operation group and T2 DM operation group）,12 in each group. The rats in normal diet group were fed on common fodder and intraperitoneally injected with critric acid buffer,and those in other two groups were fed on high fat and sugar diet and then intraperitoneally injected with STZ. The rats in T2 DM sham operation group were given sham operation,and those in T2 DM operation group were given surgical removal of the right kidney to induce the model of T2DM-induced nephropathy. The blood biochemistry indicators,blood coagulation index and urine protein were tested,and at the same time,renal lesions were observed by HE staining. Result： Weight,kidney index,fasting blood glucose（ FBG）,insulin（ INS）,creatinine clearance rate（ Ccr）,blood lipid,24-h urine protein,and TAFI levels in T2 DM operation group were obviously higher than those in other two groups. The pathological changes of the kidneys in T2 DM operation group were significantly aggravated as compared with other two groups. Conduction： The triplex process（ high fat and sugar diet ＋ unilateral nephrectomy ＋ a low dose of STZ） can establish the steady rat model which accords with the characteristics of T2DM-induced nephropathy. TAFI may participate in the development of the kidney injury induced by T2 DM in rats.