Relationship between apoptosis and change of P53 expression in mouse renal tissues after acute kidney injury
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF PATHOPHYSIOLOGY
- Issue:
- 11
- DOI:
- 10.3969/j.issn.1000-4718.2012.11.010
- Key Word:
- P53;急性肾损伤;Pifithrin-alpha;细胞凋亡;缺血再灌注
Abstract： 目的:探讨缺血再灌注致急性肾损伤(AKI)小鼠肾脏不同部位P53的表达及其与细胞凋亡的关系.方法:采用随机对照动物实验方法,将18只小鼠随机分为假手术组、AKI组及P53抑制剂pifithrin-alpha(PFT-α)组,每组6只.采用双侧肾蒂夹闭45 min后松开动脉夹的方法建立小鼠AKI模型,PFT-α组于建模前5 min腹腔注射PFT-α 2.2 mg/kg,并于建模后48 h采血检测尿素氮和肌酐,取肾脏组织行HE染色观察肾组织病理学变化,采用Western blotting法测定P53蛋白含量,免疫荧光法确定肾脏不同部位P53的表达,TUNEL法检测肾脏细胞凋亡,免疫组化方法检测肿瘤坏死因子受体(TNFR)、caspase-3及Bcl-2蛋白水平.结果:(1)PFT-α组和AKI组小鼠血尿素氮和肌酐水平均明显高于假手术组,而PFT-α组与AKI组比较血尿素氮和肌酐水平明显降低(P<0.05);肾组织HE染色显示假手术组肾组织细胞形态完整,排列整齐,无明显病理改变,AKI组肾小管上皮细胞刷状缘脱落、空泡及滴状变性,皮髓质间有明显淤血带;PFT-α组肾小管上皮部分刷状缘脱落消失,空泡及滴状变性减轻,皮髓质间无明显淤血带;(2)假手术组小鼠肾脏有少量P53表达且未检测到凋亡细胞,而AKI组小鼠缺血再灌注48 h后P53蛋白水平及凋亡细胞明显增加(P<0.05),并且均主要定位在肾皮质,PFT-α组较AKI组小鼠肾脏P53蛋白含量及凋亡细胞指数均减少(P<0.05);(3)与假手术组相比,AKI组小鼠肾脏TNFR蛋白及caspase-3蛋白水平升高(P<0.05),Bcl-2蛋白水平下降(P<0.05),PFT-α组较AKI组小鼠肾脏TNFR蛋白及caspase-3蛋白水平降低(P<0.05),Bcl-2蛋白水平升高(P<0.05).结论:急性肾损伤时,肾组织P53表达增加,主要定位于皮质,通过调控凋亡蛋白Bcl-2和TNFR的水平,促进caspase-3的释放,从而介导细胞凋亡.
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