首页|抑制自噬加重脑死亡状态下肝细胞损伤

抑制自噬加重脑死亡状态下肝细胞损伤

扫码查看
目的 探讨凋亡和自噬在脑死亡状态下肝细胞损伤中的作用.方法 将40只SD大鼠随机分为4组:对脑死亡组采用缓慢间歇颅内加压法诱导脑死亡,并且维持脑死亡状态6 h;对假手术组进行颅内置管,但是不进行脑死亡的诱导;对脑死亡+自噬抑制剂组诱导脑死亡前1 h腹腔注射自噬抑制剂3-甲基腺嘌呤(3-MA),建立并维持脑死亡状态6 h;对脑死亡+空白溶剂组诱导脑死亡前1 h腹腔注射空白溶剂二甲基亚砜(DMSO),建立并维持脑死亡状态6 h.造模完成后,取大鼠静脉血及肝脏标本.通过荧光定量qPCR检测Caspase-3 mRNA表达水平;通过Western blot检测LC3及Caspase-3蛋白表达水平;通过免疫组化检测Caspase-3蛋白在肝组织中分布和表达.结果 与假手术组相比,脑死亡组中凋亡相关基因Caspase-3表达上升,肝细胞凋亡加重;自噬相关基因LC3表达上调(P<0.05);与脑死亡+空白溶剂组相比,脑死亡组凋亡相关基因及自噬相关基因表达差异无统计学意义(P>0.05);与脑死亡+空白溶剂组相比,脑死亡+自噬抑制剂组中LC3表达下调(P<0.05),凋亡相关基因Caspase-3表达增加(P<0.05),并且肝细胞凋亡增加(P<0.05).结论 细胞凋亡参与并介导脑死亡状态下的肝细胞损伤,自噬能减轻脑死亡状态下的肝细胞损伤.
Inhibiting Autophagy Increases Hepatocellular Injury Under Brain Death State
Objective To investigate the role of apoptosis and autophagy on hepatic injuryunder brain death state.Methods The 40 SD rats were randomly divided into 4 groups:the brain death group was induced by slow intermittent intracranial compression and maintained in a state of brain death for 6 hours,perform intracranial catheterization on the sham surgery group,but did not induce brain death,inject autophagy inhibitor 3-methyladenine(3-MA)intraperitoneally into the brain death+autophagy inhibitor group 1 hour before inducing brain death,and establish and maintain a state of brain death for 6 hours,for the brain death+blank solvent group intraperitoneal injection of blank solvent dimethyl sulfoxide(DMSO)was administered 1 hour before inducing brain death,and the brain death state was established and maintained for 6 hours.After the molding was established,the venous blood and liver specimens were taken from rats.qPCR was used to detect the expression of Caspase-3 mRNA.Western blot was used to detect the expression of LC3 and Caspase-3 protein.Immunohistochemistry was used to detect the distribution and expression of Caspase-3 in liver tissues.Results Compared with sham surgery group,the expression of apoptosis-related gene Caspase-3 was up-regulated and the apoptosis of hepatocytes increased in brain death group,the expressions of autophagy-related genes LC3 were up-regulated(P<0.05).Compared with the DMSO group,there was no statistical difference in apoptosis-related genes and autophagy-related genes in brain death group(P>0.05).Compared with the DMSO group,the expression of LC3 in 3-MA group was down-regulated(P<0.05),the expression of apoptosis-related gene Caspase-3 was up-regulated(P<0.05),and the apoptosis of hepatocytes increased(P<0.05).Conclusion Apoptosis participates in and mediates the hepatocellular injury under brain death,and autophagy attenuates hepatocellular injury underbrain death state.

brain deathhepatocellular apoptosisautophagy

李月霞、石慧娟、曹胜利

展开 >

郑州大学第一附属医院 重症医学科 河南郑州 453000

郑州大学第一附属医院 肝胆胰外科,河南郑州 453000

脑死亡 肝细胞凋亡 自噬

NSFC-河南联合基金

U2004122

2024

河南医学研究
河南省医学科学院

河南医学研究

影响因子:0.979
ISSN:1004-437X
年,卷(期):2024.33(15)