全反式维甲酸对肾硬化大鼠肾脏组织α-SMA表达及细胞外基质代谢的影响

Effects of all-trans retinoic acid on the expression of α-smooth muscle actin and the metabolism of extracellular matrix in rats with glomerulosclerosis

目的探讨全反式维甲酸(ATRA)对肾硬化大鼠肾脏组织α-平滑肌肌动蛋白(α-SMA)表达、Ⅳ型胶原(ColⅣ)和纤维连接蛋白(FN)代谢的影响。方法80只雄性8周龄Wistar大鼠随机分成4组,假手术组、模型组、苯那普利组和ATRA组,每组20只。采用单侧肾切除加1周后尾静脉注射阿霉素(5 mg/kg)的方法建立肾小球硬化(GS)大鼠模型,造模后12周末处死。肾脏病理切片采用苏木素-伊红(HE)染色,计算肾小球硬化指数(GSI)。免疫组织化学方法检测肾脏组织α-SMA、ColⅣ和FN的蛋白表达,用逆转录-聚合酶链反应(RT-PCR)法检测肾脏组织α-SMA mRNA的表达。结果与模型组相比,ATRA组和苯那普利组大鼠GSI显著下降(P<0.01),肾脏组织ColⅣ、FN及α-SMA蛋白表达显著减少,肾脏组织α-SMA mRNA表达量显著下降(P<0.05),但两治疗组间差别无统计学意义(P>0.05)。结论ATRA可能通过抑制GS大鼠肾脏组织α-SMA表达,减少细胞外基质合成,最终延缓GS进展。

Objective To explore the effects of all-trans retinoic acid （ATRA） on the expression of α-smooth muscle actin （α-SMA） and the metabolism of collagen Ⅳ （Col Ⅳ） and fibronectin （FN） in rats with glomerulosclerosis （GS）. Methods Eighty 8-week-old Wistar male rats were randomly assigned into following groups, sham operated group （n = 20）, model group （n = 20）, benazepril treatment group （n = 20）, ATRA treatment group （n = 20）. The experimental rats with GS were established by uninephrectomization and injection with adriamycin （5 mg/kg） through the tail vein one week later. All rats were sacrificed at the 12 th week. GS was evaluated by glomeruloselerosis index （GSI） system. The expressions of α-SMA, Col Ⅳ and FN were detected by immunohistochemistry method. The expression of α-SMA mRNA was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results Compared to model group, ATRA and benazepril treatment groups not only had significantly reduced GSI （P 〈 0.01 ）, but also had significantly reduced the expression of α-SMA, Col Ⅳ , FN, and α-SMA mRNA （P 〈 0.05）. There was no significantly difference of GSL between ATRA and benazepril treatment groups （P 〉 0.05）. Conclusions ATRA may reduce the progression of GS through inhibiting the expression of α-SMA and the produce of extracellular matrix.