活化补体诱生一氧化氮介导肝细胞损伤的实验研究

Nitric oxide induced by activated complement mediates hepatocyte injury

目的探讨活化补体对大鼠枯否细胞KC分泌一氧化氮NO的影响及其与肝细胞损伤的关系。方法大鼠KC+肝细胞HC联合培养分别与酵母多糖活化人血清ZAHS,抗人C3、C5中和的ZAHS以及ZAHS+氨基胍iNOS抑制剂作用后,观测培养上清中不同时相点的NO和乳酸脱氢酶LDH。结果ZAHS作用组KC+HC联合培养的上清中NO和LDH各时相点的测值显著升高P<0.01;中和血清组和氨基胍组培养上清中NO分别下降53.4%～62.8%和68.1%～72.1%,LDH分别下降56.0%～66.5%和51.2%～57.2%,与作用组相差显著P<0.01。结论ZAHS中的C3、C5片断可激发KC生成NO,介导肝细胞损伤,这可能是某些病理情况下补体介导肝损伤的机制之一。

Aim To investigate whether activated complement can induce Kupffer cell(KC)secrete nitric oxide(NO)and its role in hepatocyte(HC)injury.Methods Prior -treatment of Zymosan -activated human serum(ZAHS )or ZAHS neutralized by anti -C 3 ,C 5 serum or ZAHS +aminoguanidine(AGD),NO and lactate dehydrogenatase(LDH)in su-pernatant of KC /HC co -culture were m easured in different time points.Rusults In every designed time point,in ZAHS -treated group,NO and LDH significantly rose over normal (P<0.01);Compared to ZAHS -treated group,in neutralized ZAHS -treated and ZAHS +AGD -treated group,NO and LDH decreased s harply(P<0.01),the levels of NO reduced to 53.4%～62.8%and to 68.1%～72.1%and the lev-els of LDH reduced to 56.0%～66.5%and to 51.2～57.2%;LDH significantly correlated with NO(r =0.9528).Conclusion The frag-ments of C 3 and C 5 in ZAHS can make KC secrete NO ,by whic h they mediate hepatocyte injury .It is the possible mechanism of liver injury mediated by complement in some pathological situations.