抑制乙酰转移酶p300对大鼠体外循环肺损伤及自噬的影响  

Effects of inhibition of acetyltransferase p300 on lung injury and autophagy during extracorporeal circula‐tion in rats

作　　者：张仁鸿 陈卓 吴汉华 罗俊丽 窦雪娇 张红 ZHANG Renhong;CHEN Zhuo;WU Hanhua;LUO Junli;DOU Xuejiao;ZHANG Hong(School of Graduate,Zunyi Medical University,Zunyi 563006,Guizhou,China;Anesthesia Department,Affiliat-ed Hospital of Zunyi Medical University,Zunyi 563099,Guizhou,China)

机构地区：[1]遵义医科大学研究生院,遵义563006 [2]遵义医科大学附属医院麻醉科,遵义563099

出　　处：《医学研究与战创伤救治》2025年第1期9-15,共7页Journal of Medical Research & Combat Trauma Care

基　　金：国家自然科学基金(82060083)。

摘　　要：目的探讨抑制乙酰转移酶p300对大鼠体外循环肺损伤及自噬的影响。方法18只雄性健康SD大鼠随机分为3组:假手术组(Sham组)、体外循环左肺损伤组(I/R组),体外循环左肺损伤+p300抑制剂组(C646组)。各6只。Sham组做穿刺及开胸处理,不建立CPB;I/R组及C646组建立CPB左肺损伤模型,并在CPB前10 min经尾静脉分别注射等量等渗盐水及p300选择性抑制剂C646;实验在3个时间点行血气分析,包括体外循环前(T1)、开放肺门10 min后(T2)以及实验结束时(T3),同时计算得出氧合指数(OI)和呼吸指数(RI)的值;T3时取左肺支气管肺泡灌洗液(BALF)及左侧肺组织,ELISA检测左肺BALF中TNF-α和总蛋白含量,透视电镜下观察左肺组织自噬小体和自噬溶酶体,Western blot检测肺组织p300及自噬相关蛋白Beclin1、p62表达。结果与Sham组比较,T2、T3时刻I/R组和C646组OI明显降低,RI明显升高(P<0.05)、TNF-α和总蛋白含量明显增加,I/R组p300和Beclin1、P62表达增加(P<0.05),C646组p300、Beclin1表达减少,p62表达增加(P<0.05),病理损伤评分明显升高(P<0.05),Ⅱ型肺泡上皮细胞胞浆内自噬明显;与I/R组比较,T3时刻C646组OI明显升高,RI明显降低(P<0.05),TNF-α和总蛋白含量明显降低,p300和自噬相关蛋白Beclin1、P62表达减少(P<0.05),病理损伤评分明显降低,Ⅱ型肺泡上皮细胞细胞质内自噬减少(P<0.05)。结论抑制乙酰转移酶p300后大鼠CPB后肺组织自噬蛋白Beclin1、P62表达明显减少;乙酰转移酶p300抑制剂C646可减轻肺部炎症反应,改善肺功能,可能与其抑制过度自噬有关。Objective This study aims at exploring the effects of inhibition of acetyltransferase p300 on lung injury and autophagy during extracorporeal circulation in rats.Methods Eighteen healthy male SD rats were randomly divided into three groups(n=6):Sham operation group(Sham group),left lung injury group after extracorporeal circulation(I/R group),extracorporeal circulation left lung injury+p300 inhibitor group(C646 group).The Sham group underwent puncture and thoracotomy without establishing CPB;the I/R group and the C646 group established CPB left lung injury models,and the same amount of normal saline and the p300 selective inhibitor C646 were injected through the tail vein 10 minutes before CP.Blood gas analysis was performed at three time points in the experiment,including before extracorporeal circulation(T1),10 minutes after opening the hilum(T2),and at the end of the experiment(T3).The oxygenation index(OI)and respiratory index(RI)were calculated.At T3,the bronchoalveolar lavage fluid(BALF)and left lung tissue of the left lung were collected,and the TNF-αand total protein contents in the left lung BALF were detected by ELISA.The autophagosomes and autophagolysosomes of left lung were observed under transmission electron microscope,Western-Blot detects the expression of p300 and autophagy-related proteins Beclin1 and p62 in lung tissue.Results Compared with the Sham group,OI was significantly decreased and RI was significantly increased in the I/R group and C646 group at T2 and T3(P<0.05)、TNF-αand total protein levels significantly increased,and the expression of p300,Beclin1 and P62 increased in the I/R group(P<0.05);the expression of p300 and Beclin1 decreased and the expression of p62 increased in the C646 group(P<0.05);the pathological damage score increased significantly(P<0.05);autophagy is evident in the cytoplasm of type II alveolar epithelial cells.Compare with I/R group,OI was significantly increased and RI was significantly decreased in the C646 group at T3(P<0.05);TNF-αand total protein levels

关 键 词：体外循环 肺损伤 乙酰转移酶p300 自噬 

分 类 号：R563[医药卫生—呼吸系统]