成纤维细胞生长因子21减轻小鼠肝脏缺血再灌注损伤

Fibroblast growth factor 21 alleviates liver ischemia-reperfusion injury

目的:探讨成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)对小鼠肝脏缺血再灌注(ischemia-reperfusion,IR)损伤的保护作用,并进一步研究其可能机制。方法:30只C57BL/6小鼠,随机分为3组:假手术组(sham组)小鼠仅接受开腹及关腹操作;对照组(IR+NS组)小鼠术前30 min尾静脉注射生理盐水(NS)2 m L/kg体重,制成肝脏IR损伤模型;实验组(IR+FGF21组)小鼠术前30 min尾静脉注射重组小鼠成纤维细胞生长因子21(rm FGF21)2 m L/kg体重,并制成肝脏IR损伤模型。再灌注后12 h处死小鼠,获取静脉血及肝脏组织。检测各组小鼠血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平;苏木素-伊红(HE)染色及TUNEL染色观察肝脏组织损伤情况;检测各组小鼠肝脏内丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、活性氧(reactive oxyen species,ROS)含量。结果:与IR+NS组相比较,IR+FGF21组肝组织病理损伤情况明显改善,血清ALT及AST值较低(P<0.01),肝组织MDA和ROS水平明显下降(P<0.01),SOD和GSH含量明显上升(P<0.01)。结论:FGF21能减轻小鼠肝脏缺血再灌注损伤,其机制可能与抑制肝缺血再灌注后的氧化应激反应有关。

Objective：To explore the protective effect of fibroblast growth factor 21（FGF21）on liver ischemia-reperfusion（IR）injury in mice and the possible mechanisms. Methods：Thirty C57 BL/6 mice were randomly divided into 3 groups：sham-operated group,IR＋NS group（mice were injected with 2 m L/kg saline by tail vein just before ischemia induction）and IR＋FGF21 group（mice were injected with 2 m L/kg FGF21 before operation）. The mouse partial liver model of IR injury was established. Twelve hours after reperfusion,the mice were sacrificed and the serum and liver samples undergoing IR injury were collected. The ALT and AST levels in serum were determined. Liver histological damage was evaluated with hematoxylin-eosin（HE）staining and TUNEL detection. Levels of malondialdehyde（MDA）,superoxide dismutase（SOD）,glutathione（GSH）and reactive oxygen species（ROS）in liver tissue were also determined. Results：Liver tissues in IR＋FGF21 group were more slightly damaged than those in IR＋NS group（P〈0.01）. The ALT and AST levels in IR＋FGF21 group were significantly lower than those of IR＋NS group（P〈0.01）. The levels of plasma MDA and ROS contents in IR＋FGF21 group were significantly lower than those of IR＋NS group（P〈0.01）. The levels of plasma SOD and GSH in IR＋FGF21 group were higher than those of IR ＋ NS group（P〈0.01）. Conclusion：FGF21 can alleviate liver IR injury probably by inhibiting oxidant stress in mice.