机构地区:[1]广西医科大学第一附属医院儿科,南宁530021
出 处:《现代预防医学》2010年第20期3950-3952,共3页Modern Preventive Medicine
基 金:广西科学基金项目资助(桂科自0832121)
摘 要:[目的]通过检测全长配对盒基因2(airedbox2,PAX2)和平滑肌肌动蛋白(α-smooth muscle actin,SMA)在单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾脏组织中的表达,初步探讨PAX2在肾小管间质纤维化中的作用机制。[方法]24只雄性6周龄Wistar大鼠随机分为模型组和对照组,每组12只。模型组在无菌条件下左侧背部肋下切口行左侧输尿管结扎术,对照组只探及肾包膜,不结扎输尿管。于造模后d21处死大鼠,检测血清肌酐(serum creatinine,Scr)和尿素氮(blood urea nitrogen,BUN)水平。取左侧肾脏组织做HE和Masson染色检测肾脏病理改变,计算肾小管间质纤维化指数。采用实时荧光定量PCR方法检测肾组织中PAX2 mRNA表达,免疫组织化学方法检测肾脏组织PAX2及α-SMA蛋白的表达。[结果]与假手术组比较,模型组大鼠BUN、Scr水平显著增高(P﹤0.01);肾小管间质纤维化指数显著增高(P﹤0.01)。模型组大鼠肾小管上皮细胞PAX2的蛋白以及肾间质α-SMA的蛋白表达均较对照组显著增高(P﹤0.01)。对照组大鼠肾组织中仅有少量PAX2mRNA表达,模型组PAX2的mRNA表达显著增高(P﹤0.01)。直线相关分析显示:模型组大鼠肾小管上皮细胞PAX2蛋白表达与肾间质α-SMA表达呈显著正相关(r=0.882,P﹤0.05);与肾小管间质纤维化指数BUN、Scr分别均呈显著正相关(r=0.899,0.731,0.933均P﹤0.05)。[结论]在UUO大鼠模型中,肾脏组织PAX2和α-SMA表达均显著增加。PAX2可能参与肾小管上皮细胞-肌成纤维细胞转分化,使间质中肌成纤维细胞的数量增多,引起细胞外基质(Extracellular Matrix,ECM)积聚增加,导致了小管肾间质纤维化的发生发展。[Objective] To evaluate the expression of Paired Box2(PAX2) andα-smooth muscle actin(α-SMA) in renal tissue of rats with unilateral ureteral obstruction(UUO),and initially to investigate the effects of PAX2 in renal tubulointerstitial fibrosis.[Methods] Twenty-four Wistar male rats(6-week-old) were randomly assigned into 2 groups,the control and model group.The mode group's left ureter was dissociated to be obstructed.The control group was only dissociated left ureter,and not to be obstructed.12 rats of both two group were killed at 21 th day after surgery respectively,then serum creatinine(Scr) and blood urea nitrogen(BUN) were measured.Histological changes of renal tubular interstitium were observed by HE and Masson staining to observe the renal interstial fibrosis index.The expression of PAX2 mRNA of the left renal cortex were assessed by real-time quantitative polymerase chain reaction,immunohistochemistry was performed on left renal tissue for assessing expression of PAX2 and α-smooth muscle actin(α-SMA).[Results] The fibrosis index in the model group were significantly increased as compared with control(P﹤0.01).Immunohistochemistry staining indicated that the expression of PAX2 and α-SMA in model group increased significantly compared with control group(P﹤0.01).Meanwhile,the expression lever of PAX2mRNA in model group was obviously higher than that in the control group.The expressions of PAX2 protein were significantly positive correlated with α-SMA protein,renal interstial fibrosis index,BUN and Scr(r= 0.882,0.899,0.731 and 0.933,respectively,all P﹤0.05).[Conclusion] The expression of PAX2 and α-SMA in model group increased significantly in unilateral ureteral obstruction in rats.Mayble PAX2 may play a role of tubular epithelial-myofibroblast transdifferentiation(TEMT) in unilateral ureteral obstruction in rats,as a result the number of the myofibroblast cell increased in renal interstitium,which resulted in large accumulation of Extracellular Matr
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