补体因子CD59缺乏显著加重小鼠胆汁淤积性肝损伤

Complement factor CD59 deficiency significantly aggravates cholestasis liver injury in mice

目的观察补体因子CD59缺乏在小鼠胆总管结扎(BDL)模型中对胆汁淤积性肝损伤的作用.方法 BDL诱导小鼠胆汁淤积模型,于术后第3天检测肝脏损伤相关指标.结果与野生型小鼠比较,在CD59缺乏的BDL小鼠中观察到血清谷丙转氨酶[ALT:(730.67±104.50) U/L比(311.33± 52.47) U/L,t=8.784,P< 0.01],谷草转氨酶[AST:(877.17±76.31) U/L比(454.83±45.87) U/L,t=11.620,P<0.01],总胆红素[TBIL:(244.15±32.22) U/L比(141.85±41.51) U/L,t=4.769,P<0.01]水平升高,表明CD59缺乏显著加重小鼠胆汁淤积性肝损伤.然而,两个BDL组之间C3a[(408.30±167.82)μg/L比(269.48±49.33)μg/L,t=1.587,P>0.05]和C5a[(284.43±80.88)μg/L比(212.95±13.53)μg/L,t=1.743,P>0.05]水平差异无统计学意义,表明CD59缺乏不影响体内C3和C5活化产物的产生.在CD59缺乏的小鼠肝组织中观察到膜攻击复合物(MAC)沉积量增加.结论 CD59缺乏上调了MAC的表达,导致胆汁淤积性肝损伤加重.

Objective To investigate the role of complement factor CD59 in cholestatic liver injury in mouse bile duct ligation (BDL) model. Methods The cholestasis model of mice was induced by BDL. The relevant indexes were detected 3 days after operation. Results Increased alanine aminotransferase [ALT:(730.67±104.50) U/L vs.(311.33±52.47) U/L, t=8.784, P<0.01], aspartate aminotransferase [AST:(877.17±76.31) U/L vs.(454.83±45.87) U/L, t=11.620, P<0.01], and total bilirubin [TBIL:(244.15±32.22) U/L vs.(141.85±41.51) U/L, t=4.769, P<0.01] were observed in CD59 deficient animals with BDL when compared with wildtype control, indicating that CD59 deficiency significantly aggravates cholestatic liver injury in mice. However, there was no significant difference in C3a [(408.30±167.82)μg/L vs.(269.48±49.33)μg/L, t=1.587, P>0.05] and C5a [(284.43±80.88)μg/L vs.(212.95±13.53)μg/L, t=1.743, P>0.05] levels between the two BDL groups, suggesting that CD59 deficiency did not impact in vivo generation of C3 and C5 activation products. An increased membrane attack complex (MAC) deposition in CD59 deficiency animals could be monitored. Conclusion The present study proves a functional role of CD59 during cholestasis. CD59 deficiency leads to aggravated cholestatic liver injury by up-regulating the expression of MAC. CD59 appears to be an attractive target for future therapeutic intervention in chronic cholestatic liver disease.