白细胞介素-6在大鼠肝肺综合征发病机制中的作用  

The role of IL-6 in the pathogenesis of hepatopulmonary syndrome in rats

作　　者：王立国[1] 郭月宁 刘喃喃[1] WANG Li-guo;GUO Yue-ning;LIU Nan-nan(Department of gastroenterology,Harbin Medical University,Harbin,150000,China)

机构地区：[1]哈尔滨医科大学附属第四医院消化内科,黑龙江150000 [2]哈尔滨医科大学附属第一医院

出　　处：《肝脏》2021年第2期195-198,共4页Chinese Hepatology

基　　金：黑龙江省卫生计生委科研课题(2016-127)。

摘　　要：目的阐明白细胞介素-6(IL-6)在大鼠HPS发病中的地位及作用机制。方法建立HPS大鼠模型,并分离培养大鼠肺微血管内皮细胞(PMVEC),通过PCR、Western Blot等技术研究IL-6对细胞增殖及相关信号通路的影响。结果胆总管结扎方法可建立HPS大鼠模型,4~6周形成肝硬化及HPS,表现为大鼠精神萎靡、尿黄、行动迟缓、呼吸困难、低氧血症及血浆一氧化氮(NO)浓度增高,超声示胆总管扩张,肝脏被膜不平,6 w处死大鼠观察肝脏纤维条索形成,病理见肝脏假小叶及肺微血管扩张;IL-6在大鼠HPS中明显表达,与肿瘤坏死因子-α、IL-8、IL-1等相比,P<0.05,差异有统计学意义;通过MTT及流式细胞术检测细胞增殖及凋亡水平,结果表明IL-6促进了PMVECs增殖及抑制了脂多糖诱导的PMVEC凋亡,其主要发生机制是通过激活JAK2/STAT3信号通路而实现的。结论IL-6可通过激活JAK2/STAT3信号传导通路,促进PMVECs的增殖,进而影响HPS的发生。Objective To establish a rat model of hepatopulmonary syndrome(HPS),isolate and culture pulmonary endothelium,and elucidate the role and mechanism of IL-6 in the pathogenesis of hepatopulmonary syndrome in rats.Methods We established a rat model of Hepatopulmonary Syndrome,isolated and cultured rat lung Endothelium,and studied the effects of IL-6 on cell proliferation and related signaling pathways by PCR and Western blot.Results HPS rat model was established by common bile duct ligation.Liver cirrhosis and HPS were induced in 4~6 weeks.The manifestations of HPS were listlessness,yellowing of urine,bradykinesia,dyspnea,hypoxemia and increased concentration of plasma nitric oxide,ultrasound showed that the bile duct was dilated and the membrane of the liver was uneven.6w rats were sacrificed to observe the formation of hepatic fibrous bands and the dilatation of hepatic pseudolobule and pulmonary microvessels;The expression of IL-6 in HPS was significantly higher than that in tumor necrosis factor-α,IL-8 and IL-1,P<0.05;The results showed that IL-6 could promote the proliferation of lung endothelium and inhibit the apoptosis of PMVECs induced by lipopolysaccharide(LPS),the main mechanism is through activating JAK2/STAT3 signal pathway.Conclusion IL-6 can activate JAK2/STAT3 signal transduction pathway,promote the proliferation of PMVECs,and then affect the occurrence of HPS.

关 键 词：肝肺综合征(HPS) 白细胞介素-6(IL-6) JAK2 STAT3 

分 类 号：R73[医药卫生—肿瘤]