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覃远汉, 雷凤英, 裴娟, 胡鹏, 黄韦芳, 庞玉生. 全反式维甲酸对大鼠肾脏MMPs/TIMPs影响[J]. 中国公共卫生, 2008, 24(12): 1499-1501. DOI: 10.11847/zgggws2008-24-12-45
引用本文: 覃远汉, 雷凤英, 裴娟, 胡鹏, 黄韦芳, 庞玉生. 全反式维甲酸对大鼠肾脏MMPs/TIMPs影响[J]. 中国公共卫生, 2008, 24(12): 1499-1501. DOI: 10.11847/zgggws2008-24-12-45
QIN Yuan-han, LEI Feng-ying, PEI Juan, . Effect of all-trans retinoic acid on expression of MMPs and TIMPs in rats with glomerulosclerosis[J]. Chinese Journal of Public Health, 2008, 24(12): 1499-1501. DOI: 10.11847/zgggws2008-24-12-45
Citation: QIN Yuan-han, LEI Feng-ying, PEI Juan, . Effect of all-trans retinoic acid on expression of MMPs and TIMPs in rats with glomerulosclerosis[J]. Chinese Journal of Public Health, 2008, 24(12): 1499-1501. DOI: 10.11847/zgggws2008-24-12-45

全反式维甲酸对大鼠肾脏MMPs/TIMPs影响

Effect of all-trans retinoic acid on expression of MMPs and TIMPs in rats with glomerulosclerosis

  • 摘要: 目的 观察全反式维甲酸(ATRA)对肾小球硬化(GS)大鼠肾脏基质金属蛋白酶及其组织抑制因子的影响,并探讨其作用机制.方法 80只Wistar大鼠随机分为假手术组、模型组、苯那普利组和ATRA组,每组20只.用单侧肾切除加尾静脉注射阿霉素建立GS模型,造模后12周末处死.肾脏病理切片行苏木素-伊红(HE)染色,计算肾小球硬化指数(GSI);免疫组化法检测肾组织Ⅵ型胶原(Col-Ⅳ)、纤维连接蛋白(FN)的蛋白表达;实时定量反转录-聚合酶链反应(RealtimeRT-PCR)法检测肾组织基质金属蛋白酶-2、9(MMP-2、9)及其组织抑制因子-1(TIMP-1)mRNA的表达.结果 与模型组比较,ATRA组与苯那普利组大鼠GSI均显著降低(均P<0.01),Col-Ⅳ和FN的蛋白表达均显著减少(均P<0.05),TIMP-1mRNA表达显著下调(P<0.05),MMP-2和MMP-9的mRNA表达均显著上调(均P<0.05),但2组间差异无统计学意义(P>0.05).结论 ATRA可能通过下调GS大鼠肾组织TIMP-1的表达,上调MMP-2和MMP-9的表达,促使肾小球细胞外基质(ECM)的降解增加,减少ECM积聚等机制,起到减轻GS的作用.

     

    Abstract: Objective To investigate the effect of all-trans retinoic acid on the expression of MMPs and TIMPs in rats with glomerulosclerosis and its mechanism.Methods Eighty Wistar rats were divided into four groups randomly:sham operated group,model group,benazepril group and all-trans retinoic acid(ATRA)group(n=20,respectively).The glomerulosclerosis(GS)of rats were established by uninephrectomy and adriamycin injection through tail vien.Renal pathology was elvaluated at 12th week.Immunohistochemistry was performed for renal tissue to detect collagenⅣ(Col2Ⅳ)and fibronectin(FN).Real-time reverse transcription polymerase chain reaction(RT2PCR)was used to detect the expression of MMP22,MMP29 and TIMP21 mRNA.Results ATRA and benazepril reduced glomerular sclerosis index(P<0.05,respectively) and significantly reduced Col2Ⅳ,FN protein expression and TIMP21 mRNA expression compared to model group(P<0.05).The expression of MMP22,MMP29 mRNA in ATRA and benazepril groups were enhanced obviously compared to model group(P<0.05).There was no significant difference between ATRA and benazepril treatment group(P>0.05).Conclusion ATRA can diminish the degree of glomerular sclerosis in GS rat model.The possible mechanism is through reducing the expression of TIMP21,enhancing the expression of MMP22 and MMP29 resulting in the increase of extracellular matrix degradation in glomeruli.

     

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