FK409对大鼠肝脏移植缺血再灌注损伤后JAK2/STAT3信号通路的影响

EFFECTS OF FK409 ON JAK2/STAT3 PATHWAY IN RAT LIVER TRANSPLANTATION AFTER ISCHEMIA AND REPERFUSION INJURY

目的探讨FK409对大鼠肝脏移植缺血再灌注损伤后细胞凋亡及JAK2,STAT3表达的影响。方法雄性SD大鼠60只,随机分为假手术组、生理盐水干预组、FK409干预组,采用Kamada’s袖套法建立大鼠原位肝移植模型。干预组于新肝开放前分别鼠尾静脉注射FK4092mg/kg或等量生理盐水,于24h后RT-PCR及免疫组织化学方法检测JAK2,STAT3表达水平的变化;利用原位缺口末端标记法(TUNEL法)研究肝细胞凋亡的变化。结果与生理盐水干预组相比,FK409干预组JAK2,STAT3表达明显减少(P<0.05);凋亡细胞也减少(P<0.05)。结论FK409尚能通过抑制与炎性细胞因子及氧化应激有密切关系的JAK2/STAT3信号转导通路显著减轻大鼠肝移植缺血再灌注损伤后组织损伤。

Objective To investigate the efect of FK409 on JAK2/STAT3 pathway during hepatic ischemia reperfusion injury after orthotopic liver transplantation in rats. Methods Male Sprague-Dawley rats were used as donors and recipients in orthotopic liver transplantation（OLT） and were divided into FK409 group and Saline（NS） control group randomly according to whether FK409 was injected in vein 5 minutes before liver grafts harvesting. The third group was sham operation（SO）. The animals were killed at 24 h after graft reperfusion or sham operation respectively, paraffin-embedded specimen to detect rat liver apoptosis（TUNEL） and the protein expression of JAK2 ,STAT3 （immunohistoehemical） ; Part of fresh liver tissue was collected to detect the expression of JAK2 mRNA and STAT3 mRNA by RT-PCR. Result： The apoptosis index （Al） of liver tissue and the expression of JAK2/STAT3 mRNA and protein of JAK2/STAT3 were lower in the group of FK409 than the group of NS significantly （P 〈 0.05） at 24 h after reperfusion. Conclusion FK409 may alleviates liver graft isehemia and reperfusion injury by JAK2,/STAT3 pathway.