吡格列酮对肝脏缺血再灌注损伤模型大鼠的保护作用

Protective Effect of Piglitazone in Hepatic Ischemia Reperfusion Injury Model of Rats

目的探讨吡格列酮对肝脏缺血再灌注损伤模型大鼠的保护作用及分子机制。方法 40只SD大鼠随机分成假手术组、肝脏缺血再灌注损伤组、过氧化物酶增殖酶受体-γ(PPAR-γ)激动剂吡格列酮干预组和吡格列酮+PPAR-γ拮抗剂GW9662组。观察血清中谷丙转氨酶(ALT),谷草转氨酶(AST)和乳酸脱氢酶(LDH)水平;免疫蛋白印记法检测各组肝细胞沉默信息调节因子1(SIRT1)、乙酰化p53(Acetyl 53)、p53、B淋巴细胞瘤-2基因-相关的X蛋白(Bax)、B淋巴细胞瘤-2基因(BCL-2)和细胞色素C表达水平;转移酶介导的三磷酸脱氧鸟苷-生物素刻痕末端标记(TUNEL)检测肝脏细胞凋亡;苏木精-伊红染色检测肝脏组织病理形态并评分。结果与假手术组和吡格列酮组相比,肝脏缺血再灌注损伤组和GW9662组血清ALT、AST、LDH水平,肝细胞Acetyl 53、Bax、TUNEL和细胞浆细胞色素C的表达均明显增加,而SIRT1和BCL-2表达明显降低以及肝组织病理损伤明显加重。结论吡格列酮对肝脏缺血再灌注损伤有保护作用,其作用机制与增加SIRT1去乙酰化修饰p53,减少p53激活介导的线粒体凋亡途径相关。

Objective To investigate the protective effect of piglitazone（PIG）on hepatic ischemia reperfusion injury（IRI）and its molecular mechanism.Methods Forty SD rats were randomly divided into sham operation group（Sham）,hepatic IRI,PPAR-γagonist PIG intervention group and PIG＋PPAR-γantagonist GW9662（GW）group.The levels of serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST）and lactate dehydrogenase（LDH）were observed.Western blotting was used to detect the expressions of silent information regulator 1（SIRT1）,acetylated p53（Acetyl 53）,p53,Bax,BCL-2 and cytochrome C in liver cells.TUNEL was used to evaluate the cell apoptosis.HE staining was used to examine the liver tissue damage.Results Compared with Sham and PIG groups,the levels of ALT,AST,LDH in serum,Acetyl 53,Bax,TUNEL and cytochrome C（in liver cells）were significantly increased,while the expressions of SIRT1 and BCL-2 decreased in IRI and GW groups.Conclusion PIG has a protective effect on hepatic IRI.The mechanism is possibly related to the increase of SIRT1 acetylation of p53 and less activation of the p53-mediated mitochondrial apoptotic pathway.