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目的探讨酒精性肝病中蛋白酶体活性的抑制与内质网应激间的相关性。方法乙醇处理HepG2细胞建立酒精性肝损伤体外模型。设立对照组、乙醇处理组、蛋白酶体活化剂桦木酸处理组及桦木酸加乙醇共同处理组,测定各组内质网应激标志物葡萄糖调节蛋白78(g lucose regu lation protein78,GRP78)基因表达水平的变化,同时测定蛋白酶体活性和细胞内甘油三酯含量。结果乙醇处理组蛋白酶体活性降低,GRP78表达增高,细胞内甘油三酯含量增多;而桦木酸组结果相反;蛋白酶体活性变化与GRP78表达水平呈负相关,GRP78表达水平与甘油三酯含量呈正相关。结论乙醇处理可通过抑制蛋白酶体活性诱发内质网应激;桦木酸可提高蛋白酶体活性而降低内质网应激严重程度;蛋白酶体活性变化与内质网应激严重程度呈负相关性,后者可加剧酒精性肝损伤。
Objective To investigate the relationship between inhibition of proteasome activity and endoplasmic reticulum stress in alcoholic liver disease. Methods HepG2 cells were treated with ethanol to establish an in vitro model of alcoholic liver injury. The control group, ethanol treatment group, proteasome activator betulinic acid treatment group and betulinic acid plus ethanol group were co-treated with each other, and the endoplasmic reticulum stress marker glucoseupregulation protein 78 (GRP78) Changes in levels were measured simultaneously with proteasome activity and intracellular triglyceride content. Results The activity of proteasome decreased, the expression of GRP78 increased and the level of intracellular triglyceride increased in ethanol-treated group, but reversed in betulinic acid group. The change of proteasome activity was negatively correlated with the expression of GRP78, and the expression of GRP78 was positively correlated with triglyceride . Conclusion Ethanol treatment can induce endoplasmic reticulum stress by inhibiting the activity of proteasome. Betulinic acid can increase proteasome activity and reduce the severity of endoplasmic reticulum stress. Protease activity has a negative correlation with the severity of endoplasmic reticulum stress. The latter can aggravate alcoholic liver injury.