糖基转移酶Colgalt2基因缺失对于对乙酰氨基酚导致的肝损伤的保护作用初探

Preliminary study on the protective effect of glycosyltransferase Colgalt2 gene deletion on acetaminophen-induced liver injury

目的探讨糖基转移酶Colgalt2基因缺失对于对乙酰氨基酚(APAP)导致的小鼠急性肝损伤的保护作用。方法选择Colgalt2+/+野生型小鼠20只和Colgalt2-/-小鼠20只(均为C57BL/6J品系)为研究对象,腹腔注射APAP溶液建立小鼠急性肝损伤模型,将小鼠分为4组,Colgalt2+/+野生型对照组、Colgalt2+/+野生型给药组(APAP 500 mg/kg)、Colgalt2-/-小鼠对照组、Colgalt2-/-小鼠给药组(APAP 500 mg/kg),测定生存率,绘制生存曲线,通过检测血清丙氨酸转氨酶、天冬氨酸转氨酶水平评价肝脏功能,HE染色观察肝脏组织病理变化评价肝脏损伤情况,采用Western blot对肝损伤相关蛋白c-JNK氨基末端激酶(JNK)进行检测。多组样本均数的比较用方差分析,进一步两两比较方差齐者用LSD-t检验,方差不齐者用Games-Howel法。结果与Colgalt2+/+小鼠相比,Colgalt2-/-小鼠给予APAP后,小鼠生存率明显升高(86.7%比40.0%),小鼠肝细胞死亡及炎性细胞浸润轻于Colgalt2+/+小鼠,血清丙氨酸转氨酶、天冬氨酸转氨酶水平明显降低[丙氨酸转氨酶:(5291.90±1016.34)U/L比(1616.90±330.65)U/L,P=0.000;天冬氨酸转氨酶:(4978.00±1028.43)U/L比(1851.00±437.55)U/L,P=0.000],肝组织中JNK表达水平降低。结论在APAP诱导的小鼠肝损伤中,Colgalt2基因缺失对于APAP诱导的急性肝损伤发挥保护作用,Colgalt2可能成为APAP诱导的肝毒性的潜在治疗选择。

Objective To investigate the protective effect of Colgalt2 gene deletion on acute liver injury induced by acetaminophen(APAP)in mice.Methods Colgalt2+/+wild-type control mice and Colgalt2-/-mice(all C57BL/6J strains)were selected as the research subject.APAP solution was injected intraperitoneally to establish a mouse model of acute liver injury.The mouse were divided into four groups:Colgalt2+/+wild-type control group,Colgalt2+/+wild-type drug group(APAP 500 mg/kg),Colgalt2-/-control group,and Colgalt2-/-drug group(APAP 500 mg/kg).The survival rate was measured to plot survival curve.Liver function was evaluated by detecting serum ALT and AST levels.Liver histopathological changes were observed by HE staining to evaluate the condition of liver injury.Western blot was used to detect protein c-Jun N-terminal kinase(JNK)-related liver injury.Results Compared with Colgalt2+/+mice,the survival rate was significantly increased after giving APAP to Colgalt2-/-mice(86.7%vs.40%),and liver cell necrosis and inflammatory cell infiltrates of Colgalt2+/+mice were milder.Serum ALT,and AST level was significantly decreased[ALT:(5291.9±1016.34)U/L vs.(1616.9±330.65)U/L,P=0.000;AST:(4978.0±1028.43)U/L vs.(1851.0±437.55)U/L,P=0.000].The expression level of JNK was significantly decreased in liver tissue.Conclusion Colgalt2 gene deletion has a protective effect on acute liver injury induced by acetaminophen(APAP)in mice.Therefore,Colgalt2 may be a potential therapeutic option for acetaminophen-induced hepatotoxicity.