体外循环致大鼠肺损伤与乙酰转移酶p300的关系
Relationship between lung injury caused by cardiopulmonary bypass and acetyltransferase p300 in rats
曾祥丽 1罗俊丽 2陈松 2周雯静 2张红2
作者信息
- 1. 遵义医科大学附属医院麻醉科,遵义563000;成都市温江区人民医院麻醉科,成都 611100
- 2. 遵义医科大学附属医院麻醉科,遵义563000
- 折叠
摘要
目的 评价体外循环(CPB)致大鼠肺损伤与乙酰转移酶p300(p300)的关系.方法 SPF级健康雄性SD大鼠18只,12～16周龄,体质量350～450 g,采用随机数字表法分为3组(n=6):假手术组(S组)、CPB组和CPB+左肺缺血再灌注组(CPB+IR组).CPB+IR组在CPB过程中采用夹闭左肺门45 min后开放的方法制备肺缺血再灌注损伤模型,30 min后停止CPB,继续机械通气1.5 h后结束实验.分别于CPB前、开放肺门后10 min和实验结束即刻行动脉血气分析,计算氧合指数(OI)和呼吸指数(RI).实验结束即刻收集大鼠左肺支气管肺泡灌洗液(BALF)及左肺组织,采用ELISA法检测BALF IL-6、TNF-α、总蛋白和肺组织IL-17浓度,采用Western blot法检测肺组织p300、磷酸化p300(p-p300)和乙酰化组蛋白H3(AC-H3)表达,免疫组化染色法检测肺组织p-p300表达,光镜下观察肺组织病理学结果,并行病理损伤评分.结果 与S组比较,CPB组和CPB+IR组开放肺门后10 min和实验结束即刻OI降低,RI升高,肺组织病理损伤评分、BALF IL-6、TNF-α、总蛋白和肺组织IL-17水平升高,p300、p-p300和AC-H3表达上调(P＜0.05);与CPB组比较,CPB+IR组开放肺门后10 min和实验结束即刻OI降低,RI升高,肺组织病理损伤评分、BALF IL-6、TNF-α、总蛋白和肺组织IL-17水平升高,肺组织p300、p-p300和AC-H3表达上调(P＜0.05).结论 CPB致大鼠肺损伤的机制可能与肺组织p300表达上调和活性增强,炎症因子释放增加有关.
Abstract
Objective To evaluate the relationship between lung injury induced by cardiopulmo-nary bypass(CPB)and acetyltransferase p300(p300)in rats.Methods Eighteen SPF healthy adult male Sprague-Dawley rats,aged 12-16 weeks,weighing 350-450 g,were divided into 3 groups(n=6 each)using a random number table method:sham operation group(S group),CPB group,and CPB+left lung is-chemia-reperfusion(I/R)group(CPB+IR group).CPB group was connected to CPB pipeline for cardiopul-monary bypass.The lung I/R injury model was prepared by clamping the left lung hilum for 45 min followed by opening during CPB,30 min later CPB was terminated,and mechanical ventilation was continuously per-formed for 1.5 h before ending the experiment in CPB+IR group.Arterial blood gas analysis was performed and oxygenation index(OI)and respiratory index(RI)were calculated before CPB,at 10 min after open-ing the lung hilum,and immediately after the end of experiment.The bronchoalveolar lavage fluid(BALF)and left lung tissues were collected immediately after the end of experiment for determination of the concen-trations of interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in BALF and total protein in BALF and concentrations of IL-17 in lung tissues(by enzyme-linked immunosorbent assay),expression of p300,phosphorylated p300(p-p300),and acetylated histone H3(AC-H3)in lung tissues(by Western blot)and expression of p-p300(using immunohistochemical staining)and for microscopic examination of the pathological changes of lung tissues(under the light microscope)which were scored.Results Com-pared with S group,OI was significantly decreased and RI was increased at 10 min after opening the lung hi-lum and immediately after the end of experiment,the lung injury score and levels of IL-6,TNF-α and total protein in BALF and IL-17 in lung tissues were increased,and the expression of p300,p-p300 and AC-H3 was up-regulated in CPB and CPB+IR groups(P＜0.05).Compared with CPB group,OI was significantly decreased and RI was increased at 10 min after opening the lung hilum and immediately after the end of ex-periment,the lung injury score and levels of IL-6,TNF-α and total protein in BALF and IL-17 in lung tis-sues were increased,and the expression of p300,p-p300 and AC-H3 was up-regulated in CPB+IR group(P＜0.05).Conclusions The mechanism by which CPB induces lung injury may be related to up-regula-tion of the expression of p300 and enhancement of activity of p300 in lung tissues and increased release of inflammatory factors in rats.
关键词
体外循环/急性肺损伤/乙酰转移酶Key words
Cardiopulmonary bypass/Acut lung injury/Acetyltransferases引用本文复制引用
出版年
2024
NETL
NSTL
维普
万方数据