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目的 探讨胎儿肉瘤样酪氨酸激酶1(FLT-1)启动子携带蛋白C(PC)基因的重组腺病毒(Ad-FLT-1/PC)对糖尿病肾病动脉粥样硬化大鼠模型血管壁细胞凋亡及氧化应激的作用.方法 采用高糖、高脂饮食联合链脲佐菌素腹腔注射的方法构建糖尿病肾病动脉粥样硬化大鼠模型.大鼠被随机分为3组:Ad-FLT-1/PC组(n=23);空腺病毒(Ad-GFP,n=23)组;生理盐水对照(NC,n=22)组,分别经尾静脉注射Ad-FLT-1/PC、Ad-GFP及生理盐水300μl.另设健康SD大鼠(n=23)为健康对照组.分别于干预后第1、3、7、14天随机处死大鼠,Tunel法检测大鼠颈动脉血管壁细胞凋亡情况;分别用WST及TBA法检测血浆氧化应激指标超氧化物歧化酶(SOD)及丙二醛(MDA)含量.结果 Tunel染色结果显示,Ad-FLT-1/PC组、Ad-GFP组和NC组大鼠各时间点均可观察到血管壁凋亡细胞,但各时间点各组间细胞凋亡指数的差异无统计学意义(均P>0.05).至转染第14天,与Ad-GFP组和NC组相比,Ad-FLT-1/PC组大鼠血浆SOD含量升高,MDA含量下降(均P<0.05).结论 Ad-FLT-1/PC不能调控糖尿病肾病动脉粥样硬化大鼠血管壁细胞凋亡的发生,但可调控其氧化应激反应.

Objective To observe the effect of recombinant adenovirus-mediated the fms-like tyrosine kinast-1 (FLT-1) gene promoter carrying protein C (PC) gene (Ad-FLT-1/PC) on apoptosis and oxidative stress in rat with diabetic nephropathy atherosclerosis. Methods High sugar, high fat diet and streptozotocin by intraperitoneal injection were used to establish diabetic nephropathy atherosclerosis rat model. The rats were randomly divided into Ad-FLT-1/PC group (n=23), Ad-GFP group (n=23) and normal saline group (n=22) and injected with 300 ul Ad-FLT-1/PC, Ad-GFP and normal saline by caudal vein. Another healthy rats (n=23) were control group. At day 1, 3, 7 and 14 after transfection, rats of each group were randomly executed to observe vascular apoptosis and assay the level of SOD and MDA in plasma by the kit method of WST and TBA. Results Vascular cell apoptosis was observed in Ad-FLT-1/PC group, Ad-GFP group and NS group, the apoptosis index showed no statistical difference between three groups at each time point (P>0.05). At day 14 after transfection, Ad-FLT-1/PC group rats had higher concentration of the plasma SOD and lower MDA than Ad - GFP group and NS group. The difference were statistically significant (all P<0.05). Conclusions The recombinant adenovirus Ad-FLT-1/PC can effectively regulate oxidative stress but not apoptosis.