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-  2017 

内质网应激抑制剂4-PBA预处理对脑死亡致供肝细胞凋亡的影响及临床意义 Effect of Endoplasmic Reticulum Stress on Hepatocyte Apoptosis Under Brain Death

Keywords: 脑死亡,肝脏,内质网应激,蛋白磷酸酯酶2A,凋亡

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Abstract:

目的:探讨脑死亡时肝脏组织内内质网应激的活化对供肝质量的影响及其机制。方法:健康成年雄性SD大鼠30只,随机分为假手术组(S组)、脑死亡组(BD组)及脑死亡+内质网应激抑制剂4-苯丁酸(4-PBA)组(PBA组),每组10只。S组大鼠麻醉后行股动脉置管、颅骨钻孔置管及气管插管,但不行颅内加压。BD组大鼠行股动脉置管、颅骨钻孔置管及气管插管,采用渐进式颅内加压的方式建立大鼠脑死亡模型。PBA组在脑死亡模型建立后腹腔注射给予内质网应激抑制剂4-PBA。S组大鼠维持麻醉6h,BD、PBA组大鼠脑死亡维持6h后分别取各组大鼠肝脏标本行TUNEL凋亡检测及Western Blot检测内质网应激相关蛋白及蛋白磷酸酯酶2A(PP2A)表达量。结果:TUNEL凋亡检测:与S组相比,BD组及PBA组肝脏细胞凋亡率明显升高,且BD组凋亡率明显高于PBA组。Western Blot检测:与S组相比,BD组及PBA组肝脏标本内质网应激相关蛋白CHOP、ATF6及Grp78表达量均明显升高,且BD组明显高于PBA组。而BD组及PBA组PP2A磷酸化水平明显降低,且PBA组明显低于BD组。结论:脑死亡时供肝细胞凋亡增加,同时内质网应激及PP2A活性均升高,抑制内质网应激的活化程度后PP2A活性也出现下降,提示内质网应激可能是通过PP2A导致肝细胞凋亡

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