摘要
目的研究肝大部分切除术(PHx)后核受体Nur77调控肝细胞进入增殖周期的分子机制。方法在Nur77基因敲除型(knockout,KO)和野生型对照组中构建PHx诱导的小鼠肝再生模型,用组织学染色、生化、定量PCR以及蛋白免疫印迹(western-blot,WB)等方法检测再生肝组织的形态学、血清学改变,以及相应基因的表达情况。结果PHx术后多个时间点KO组肝脏均出现组织坏死,KO组术后48 h、72 h的血清ALT均高于WT组(466.3±202.4 vs 72.0±58.8,486.2±156.3 vs 63.0±0.3,P<0.05)。凋亡细胞特异性染色示KO组术后3 h和48 h的凋亡细胞计数高于对照组(38.7±9.6 vs 2.8±0.2,87.3±19.4 vs 8.4±3.1,P<0.05)。PHx术后早期KO组肝脏的凋亡基因caspase-8与剪切caspase-3蛋白均上调。结论Nur77缺失诱导肝再生早期肝细胞凋亡。
Objective To investigate the role of Nur77 on triggering cell proliferation induced by partial hepatectomy(PHx).Methods PHx was performed on Nur77 knockout(KO)mice and its wild type(WT)counterparts.Histological analysis,mRNA and protein level of relevant genes were detected.Results KO mice demonstrated more liver injury individuals than that of the controls at various time points after PHx.Consistently,the serum ALT level of KO group increased comparing with its control counterparts(466.3±202.4 vs 72.0±58.8,486.2±156.3 vs 63.0±0.3,P<0.05)Apoptosis specific staining of the liver slides 3 and 48 hours after PHx showed more positive nucleus in the KO livers than those in the controls(38.7±9.6 vs 2.8±0.2,87.3±19.4 vs 8.4±3.1,P<0.05).Correspondingly,the induction of both caspase-8 mRNA and cleaved caspase-3 protein,which is associated with apoptosis,was upregulated in the KO livers at early stage of liver regeneration.Conclusion Nur77 dificiency induced apoptosis of regenerating livers.
作者
詹琪
缪旋
聂玉强
HAN Qi;MIAO Xuan;NIE Yuqiang(Department of Gastroenterology&Hepatology,Guangzhou First People's Hospital,Guangzhou 510180,China)
出处
《广州医药》
2019年第6期7-10,59,共5页
Guangzhou Medical Journal
基金
广东省医学科学技术研究基金项目(A2016098)
广东省自然科学基金项目(2016A030310110)
关键词
肝再生
Nur77
核受体
凋亡
肝损伤
Liver regeneration
Nur77
Nuclear receptor
Apoptosis
Liver injury
