Apobec-1重组腺病毒治疗肾性高脂血症的实验研究

Experimental study of Apobec-1 recombinant adenovirus in treatment of renal hyperlipemia

目的探讨肝脏获得性表达载脂蛋白B编辑催化多肽-1(Apobec-1)对肾性血脂代谢紊乱的调控效应。方法30只健康普通级雄性新西兰兔随机分为假手术组、肾病组、Apobec-1治疗组,每组10只。肾病组、Apobec-1治疗组适应性喂养1周后行左肾切除术,术后1周耳缘静脉注射阿霉素(4 mg/kg)构建肾病模型。术后11周Apobec-1治疗组耳缘静脉注射Apobec-1重组腺病毒(1×1013病毒颗粒/kg)。术后12周处死所有兔,并摘除右侧肾脏和肝脏,分别留取血液及24 h尿液,检测24 h尿蛋白(24UPr)、白蛋白(Alb)、尿素氮(BUN)、肌酐(Cr)、血脂等指标,HE染色观察肾脏病理,Western blot检测肝脏Apobec-1、载脂蛋白B48(Apo B48)蛋白表达水平。结果 1与假手术组比较,肾病组24UPr、BUN、Cr、总胆固醇(TC)、总三酰甘油(TG)、极低密度脂蛋白(VLDL-C)、低密度脂蛋白(LDL-C)、载脂蛋白B100(Apo B100)明显升高(P<0.05),而Alb水平明显下降(P<0.05);2与肾病组比较,Apobec-1治疗组TC、TG、VLDL-C、LDL-C、Apo B100、Apo B48水平明显下降(P<0.05);3与假手术组比较,Apobec-1治疗组24UPr、BUN、Cr明显升高(P<0.05),而Alb、Apo B48明显下降(P<0.05);4 Western blot结果显示,与假手术组、肾病组比较,Apobec-1治疗组肝脏Apobec-1、Apo B48表达明显上调(P<0.01)。结论肾性高脂血症中,肝脏获得性表达Apobec-1,重建Apo B mRNA编辑,增加Apo B48-脂蛋白的合成,进而起到一定的降脂效应。

Objective To explore the effect of the liver acquired expression of apolipoprotein B editing catalytic polypeptide-1 （Apobec-1） on hyperlipidemia of renal disease. Methods Thirty healthy ordinary level male New Zealand rabbits were randomly divided into three groups： sham operation group, nephropathy group, and Apobec-1 treatment group （Each group has 10 rabbits）. Adapt feeding for one week, nephropathy group and Apobec-1 treat-ment group underwent left nephrectomy, and one week later, adriamycin （4 mg / kg） was used to construct the ne-phropathy model by ear vein injection. The eleventh week after operation, apobec-1 recombinant adenovirus （1 × 1013 Virus/ kg） was injected by ear vein in apobec-1 treatment group. The twelfth week after operation, all rabbits were sacrificed. Right kidney, liver, blood and 24h urine were left. In three groups, 24 hour urinary protein （24UPr）, albumin （Alb）, blood urea nitrogen （BUN）, creatinine （Cr）, blood lipid were detected. Renal pa-thology was observed by HE staining. Expressions of liver apobec-1, apolipoprotein B48（ApoB48）were observed by Western blot. Results ① Compared with the sham operation group, nephropathy group showed that 24UPr, BUN, Cr, total cholesterol （TC）, total triglyceride （TG）, very low density lipoprotein （VLDL-C）, low density lipoprotein （LDL-C）, apolipoprotein B100 （ApoB100） were increased（P 〈 0. 05）, but Alb was decreased（P 〈0. 05）. ② Compared with the nephropathy group, Apobec-1 treatment group showed that TC, TG, VLDL-C, LDL-C, ApoB100, ApoB48 were decreased（P 〈 0. 05）. ③ Compared with the sham operation group, Apobec-1 treat-ment group showed that 24UPr, BUN, Cr were increased（ P 〈 0. 05）, but Alb, ApoB48 were decreased（ P 〈0. 05）. ④ Compared with the sham operation group and nephropathy group, Apobec-1 treatment group showed that the expression of Apobec-1 and ApoB48 were up-regulated （P 〈 0. 01）. Conclusion When liver aquires expres-sion of Apobec-1 in hyperlipidemia of renal disease, it can reconstruct ApoB mRNA, increase the synthesis of ApoB48-lipoprotein, and play a certain lipid-lowering effect.