第Ⅴ结构域缺失型β_2-GPI对糖尿病大鼠尿蛋白排泄的影响

Effect of Domain Ⅴ Deletion of β_2-Glycoprotein Ⅰ on Urine Protein Excretion of Diabetic SD Rats

目的:探讨第Ⅴ结构域缺失型β2-糖蛋白I(DI-IV)对糖尿病大鼠24h尿蛋白排泄以及血管内皮生长因子(VEGF)-一氧化氮(NO)轴的影响。方法:将大鼠高脂喂养8周后尾静脉注射STZ(30mgkg-1)进行糖尿病造模,造模成功1周后将大鼠随机分为对照组、β2糖蛋白(Iβ2-GPI)组以及DI-IV组,每周分别于尾静脉注射人血清白蛋白(HSA)、β2-GPI、DI-IV各200mgkg-1,持续4周。于干预前后取血,测定血肌酐(Scr)、尿素氮(BUN)、血甘油三酯(TG)、总胆固醇酯(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、24h尿白蛋等。采用Westernblot检测肾脏VEGF、内皮源性一氧化氮合酶(eNOS)的表达及eNOS磷酸化。结果:与干预前相比,对照组、β2-GPI组TG、TC、LDL-C、HDL-C、Scr无明显变化(P均>0.05),而血糖、24h尿蛋白排泄升高(P均<0.05);干预后DI-IV组血TC、LDL-C、24h尿蛋白排泄均减少(P均<0.05)。与对照相比,DI-IV组肾脏VEGF-A表达减少(P<0.05),eNOS的磷酸化表达增加(P<0.05)。结论:DI-IV可能通过改善糖尿病大鼠肾脏VEGF-NO轴功能以及降脂作用,减轻糖尿病SD大鼠24h尿蛋白的排泄。

Objective： To investigate effect of domain V deletion of β2-glycoprotein I （DI-IV） on 24-hour urinary protein excretion ,VEGF-NO axis,and possible mechanisms in diabetic rats.Methods： Diabetic model was established with the use of SD rats, treated with intravenous injection of STZ （30mg/ kg） after a high fat diet for eight weeks. One week after successful modeling, the rats were randomly assigned to contro（ group, 32 glycoprotein I （β2-GPI） group and DI-IV group, treated with intravenous injection of human serum albumin （HSA）, β2-GPI or DI-IV with a dose of 200mg/kg every week ,for four weeks, respectively. Blood samples were taken before and after the intervention, and serum creatinine （Scr）, blood urea nitrogen （BUN）, serum triglyceride （TG）, total cholesterol ester （TC）, low- density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, and 24-hour urinary protein were analyzed. Western blot was used to analyze the expression of VEGF and endothelial nitric oxide synthase （eNOS）, and the phosphorylation of eNOS of rats＇ kidneys.Results： After intervention,TG,TC,HDL-C,Scr and LDL-C had no significant difference （p〉 0.05） while blood glucose and 24-hour urinary protein excretion increased （p 〈0.05） in control group and β2-GPI group;＇lC,LDL-C, 24-hour urinary protein excretion decreased （p 〈0.05） in DI-IV group. VEGF-A expression in kidneys decreased more and phosphorylation of eNOS increased more in DI-IV group than in control group （p 〈0.05）. Conclusion： DI-IV could relieve 24-hour urine protein excretion of diabetic SD rats. Possible mechanisms are to improve VEGF-NO axis function and lipid-lowering effect in diabetic rat kidneys.