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目的探讨TNF受体相关因子基因缺失导致肝功能衰竭的可能性及其可能原因。方法实验鼠分为TNF受体相关因子2(TRAF2)基因缺陷鼠TRAF2~(lox/lox)/Cre~+组、对照鼠TRAF2~(lox/lox)/Cre~-组、敲除TNF基因的TRAF2基因缺陷鼠TRAF2~(lox/lox)/Cre~+/TNF~(-/-)组和对照鼠TRAF2~(lox/lox)/Cre~-/TNF(-/-)组,用PolyI:PolyC诱导敲除TRAF2基因,动态观察血清ALT的变化,观察肝组织病理学改变。胶原酶分离肝细胞,流式细胞术(FACS)检测Fas和CD40的表达,肝细胞加TNF培养后计算存活肝细胞的比率。结果TRAF2~(lox/lox)/Cre~+组鼠于注药后第2天ALT开始升高,第4天达高峰,为(234.80±12.34)U/L,TRAF2~(lox/lox)/Cre~+/TNP(-/-)组鼠ALT亦有升高,为(90.30±15.63)U/L,但病理组织学显示前者有明显的肝细胞坏死和炎性细胞浸润。培养的TRAF2~(lox/lox)/Cre~+/TNF~(-/-)组鼠肝细胞在加入TNF后存活细胞明显低于对照鼠TRAF2~(lox/lox)/Cre~-/ TNF~(-/-)组,且前者Fas表达高于后者,而CD40表达低于后者。结论TRAF2基冈的缺失可导致肝细胞坏死,从而引起暴发性肝功能衰竭。
Objective To explore the possibility of the failure of TNF receptor related factor gene leading to liver failure and its possible reasons. Methods The experimental mice were divided into three groups: TRAF2 ~ (lox / lox) / Cre ~ + group and TRAF2 ~ (lox / lox) / Cre ~ - group with TNF receptor related factor 2 (TRAF2) TRAF2 ~ (lox / lox) / Cre ~ + / TNF ~ (- / -) group and TRAF2 ~ (lox / lox) / Cre ~ - / TNF group in TRAF2- PolyC induced knockout of TRAF2 gene, dynamic observation of ALT changes in serum, observe the pathological changes of liver tissue. Hepatic cells were separated by collagenase, the expression of Fas and CD40 was detected by flow cytometry (FACS), and the ratio of viable hepatocytes was calculated after culturing hepatocytes with TNF. Results The ALT of TRAF2 ~ (lox / lox) / Cre ~ + group increased on the 2nd day after injection and reached its peak on the 4th day (234.80 ± 12.34) U / L, TRAF2 ~ (lox / lox) The ALT in Cre ~ + / TNP (- / -) group also increased, which was (90.30 ± 15.63) U / L, but histopathology showed that the former had obvious hepatocyte necrosis and inflammatory cell infiltration. The number of viable cells in TRAF2 ~ (lox / lox) / Cre ~ + / TNF ~ (- / -) group was significantly lower than that in control group (- / -) group, and the former Fas expression is higher than the latter, while the CD40 expression is lower than the latter. Conclusions The absence of TRAF2 basal ganglia can lead to necrosis of liver cells and cause fulminant hepatic failure.