肾病综合征兔肝脏获得性表达apobec-1降脂效应及可能机制
신병종합정토간장획득성표체apobec-1강지효응급가능궤제
The lipid-lowering effect and possible mechanism of apobec-1 in nephrotic syndrome rabbits
  • 万方数据
    中华实用儿科临床杂志 중화실용인과림상잡지
    Journal of Applied Clinical Pediatrics
    2015年 17期 1317-1320 ,共4页

    孔海波%胡波%胡鹏

    공해파%호파%호붕

    低密度脂蛋白受体%低密度脂蛋白受体相关蛋白%肾病综合征%apobec-1 低密度脂蛋白受體%低密度脂蛋白受體相關蛋白%腎病綜閤徵%apobec-1
    저밀도지단백수체%저밀도지단백수체상관단백%신병종합정%apobec-1
    Low density lipoprotein receptor%Low density lipoprotein receptor related protein%Nephrotic syndrome%apobec-1
    目的 观察肝脏获得性表达apobec-1对肾病综合征(NS)兔血脂代谢及肝脏低密度脂蛋白受体(LDLR)、低密度脂蛋白受体相关蛋白(LRP)表达的影响,探讨NS兔apobec-1降脂效应及其可能机制.方法 30只健康雄性普通级新西兰兔随机分为假手术组、NS组、apobec-1治疗组,每组10只.NS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NS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,留取血液及24 h尿液,检测24 h尿蛋白(24UPr)、清蛋白(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LDLR、LRP蛋白表达水平.结果 1.假手术组、NS组及apobec-1治疗组3组之间比较显示24UPr(F=42.778,P=0.000)、Alb(F=3.819,P=0.034)、BUN(F=6.562,P=0.005)、Cr(F=16.076,P=0.000)、总胆固醇(TC,F=17.531,P=0.000)、三酰甘油(TG,F=6.192,P=0.006)、极低密度脂蛋白(VLDL-C,F=6.192,P=0.006)、低密度脂蛋白(LDL-C,F=34.924,P=0.000)、载脂蛋白B100(ApoB100,F=5.180,P=0.012)、载脂蛋白B48(ApoB48,F=6.161,P=0.006)差异均有统计学意义.2.与假手术组比较,NS组24UPr、BUN、Cr、TC、TG、VLDL-C、LDL-C、ApoB100明显升高,而Alb明显降低,差异均有统计学意义(P均＜0.05).3.与NS组比较,apobec-1治疗组TC、TG、VLDL-C、LDL-C、ApoB100、ApoB48明显降低,差异均有统计学意义(P均＜0.05).4.与假手术组比较,apobec-1治疗组24UPr、BUN、Cr明显升高,而Alb、ApoB48明显降低,差异均有统计学意义(P均＜0.05).5.Western blot结果显示3组之间LRP(F=44.180,P=0.000)、LDLR(F=63.141,P=O.000)差异具有统计学意义,与假手术组、NS组比较,apobec-1治疗组肝脏LDLR蛋白表达明显下调(P＜0.01、0.05);LRP蛋白表达明显上调(P均＜0.01).结论 NS肝脏获得性表达apobec-1可通过上调LRP,加速ApoB48-脂蛋白的清除,进而起到一定降脂效应.
    목적 관찰간장획득성표체apobec-1대신병종합정(NS)토혈지대사급간장저밀도지단백수체(LDLR)、저밀도지단백수체상관단백(LRP)표체적영향,탐토NS토apobec-1강지효응급기가능궤제.방법 30지건강웅성보통급신서란토수궤분위가수술조、NS조、apobec-1치료조,매조10지.NS조、apobec-1치료조괄응성위양1주후행좌신절제술,술후1주이연정맥주사아매소(4 mg/kg)구건NS모형;술후11주apobec-1치료조이연정맥주사apobec-1중조선병독(1×1013병독과립/kg).술후12주처사소유토,병적제우측신장화간장,류취혈액급24 h뇨액,검측24 h뇨단백(24UPr)、청단백(Alb)、뇨소담(BUN)、기항(Cr)、혈지등지표,HE염색관찰신장병리,Western blot검측간장LDLR、LRP단백표체수평.결과 1.가수술조、NS조급apobec-1치료조3조지간비교현시24UPr(F=42.778,P=0.000)、Alb(F=3.819,P=0.034)、BUN(F=6.562,P=0.005)、Cr(F=16.076,P=0.000)、총담고순(TC,F=17.531,P=0.000)、삼선감유(TG,F=6.192,P=0.006)、겁저밀도지단백(VLDL-C,F=6.192,P=0.006)、저밀도지단백(LDL-C,F=34.924,P=0.000)、재지단백B100(ApoB100,F=5.180,P=0.012)、재지단백B48(ApoB48,F=6.161,P=0.006)차이균유통계학의의.2.여가수술조비교,NS조24UPr、BUN、Cr、TC、TG、VLDL-C、LDL-C、ApoB100명현승고,이Alb명현강저,차이균유통계학의의(P균＜0.05).3.여NS조비교,apobec-1치료조TC、TG、VLDL-C、LDL-C、ApoB100、ApoB48명현강저,차이균유통계학의의(P균＜0.05).4.여가수술조비교,apobec-1치료조24UPr、BUN、Cr명현승고,이Alb、ApoB48명현강저,차이균유통계학의의(P균＜0.05).5.Western blot결과현시3조지간LRP(F=44.180,P=0.000)、LDLR(F=63.141,P=O.000)차이구유통계학의의,여가수술조、NS조비교,apobec-1치료조간장LDLR단백표체명현하조(P＜0.01、0.05);LRP단백표체명현상조(P균＜0.01).결론 NS간장획득성표체apobec-1가통과상조LRP,가속ApoB48-지단백적청제,진이기도일정강지효응.
    Objective To observe the effect of liver acquired expression of apobec-1 on blood lipid metabolism, hepatic low density lipoprotein receptor (LDLR), and hepatic low density lipoprotein receptor related protein (LRP) in nephrotic syndrome(NS) rabbits and to explore the lipid-lowering effect and possible mechanism.Methods Thirty healthy ordinary level male new Zealand rabbits were randomly divided into 3 groups:sham operation group (n =10), N S group (n =10), and apobec-1 treatment group (n =10).Adaptive feeding was given for 1 week, then NS group and apobec-1 treatment group underwent left nephrectomy,and 1 week later,adriamycin (4 mg/kg) was used to construct the NS model by way of ear vein injection.In the 11th week after operation, apobec-1 recombinant adenovirus (1 × 1013 virus/kg) was injected through ear vein in apobec-1 treatment group.The 12th week after operation, all rabbits were sacrificed.Right kidney, liver, blood and 24 hour urine were collected.In 3 groups, 24 hour urinary protein (24UPr), albumin (Alb), blood urea nitrogen (BUN), creatinine (Cr), blood lipid were detected.Renal pathology was observed by means of HE staining.Expressions of liver LDLR, LRP were observed by using Western blot.Results (1) There were significant differences among the 3 groups in 24UPr (F =42.778, P =0.000), Alb (F =3.819, P =0.034), BUN (F =6.562, P =0.005), Cr (F =16.076, P =0.000), total cholesterol (TC) (F =17.531, P =0.000), total triglyceride (TG) (F =6.192, P =0.006), very low density lipoprotein (VLDL-C) (F =6.192, P =0.006), low density lipoprotein (LDL-C) (F =34.924, P =0.000) and apolipoprotein B100 (ApoB100) (F =5.180, P =0.012) and apolipoprotein B48 (ApoB48) (F =6.161, P =0.006).(2) Compared with the sham operation group, NS group showed that 24UPr, BUN, Cr, TC, TG, VLDL-C, LDL-C, ApoB100 increased, but Alb decreased, and there was statistical significance (all P ＜ 0.05).(3) Compared with NS group, apobec-1 treatment group showed that TC, TG, VLDL-C, LDL-C, ApoB 100, ApoB48 decreased, and there were statistical significances (all P ＜ 0.05).(4) Compared with the sham operation group, apobec-1 treatment group showed that 24UPr, BUN, Cr increased, but Alb, apolipoprotein B48 (ApoB48) decreased, there were statistical significances (all P ＜ 0.05).(5) There were significant differences of hepatic protein expression among the 3 groups in LRP (F =44.180, P =0.000), LDLR (F =63.141 ,P =0.000).Compared with the sham operation group and NS group, apobec-1 treatment group showed that the expression of LRP was up-regulated (P ＜ 0.01,0.05), while the expression of LDLR was down-regulated (all P ＜ 0.05).Conclusions When liver acquired expression of apobec-1 in NS, it could up-regulate LRP,accelerate the elimination of ApoB48-lipoproteins, and produce a certain lipid-lowering effect.
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