摘要
目的:探讨肌醇依赖酶1(inositol-requiring enzyme 1,IRE1)/剪切型X-盒结合蛋白1(spliced X-box binding protein 1,sXBP1)通路特异性抑制剂STF-083010在小鼠肝脏缺血再灌注损伤中的保护作用及其可能机制。方法:选取健康清洁级雄性C57BL/6小鼠30只,随机分成假手术组(sham组)、肝缺血再灌注组(IR组)和STF-083010预处理+肝缺血再灌注组(IR+STF-083010组),每组10只。通过酶联免疫吸附试验(ELISA法)检测小鼠血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平;HE染色及TUNEL染色检测肝组织损伤情况及肝细胞的凋亡情况;实时定量PCR法检测肝组织中白细胞介素(interleukin,IL)-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α、IL-1βmRNA水平;免疫组织化学法检测肝组织中sXBP1蛋白表达水平,蛋白印迹法检测肝组织中sXBP1、转录因子C/EBP同源蛋白(C/EBPhomologous protein,CHOP)蛋白表达水平。结果:与IR组相比,IR+STF-083010组小鼠血清ALT、AST水平明显降低(P<0.01),组织学上,肝损伤情况得到明显改善(P<0.01),肝组织中IL-6、TNF-α、IL-1βmRNA水平及s XBP1、CHOP蛋白水平明显降低(P<0.01)。结论:STF-083010预处理可通过抑制s XBP1/CHOP通路减轻肝脏缺血再灌注损伤。
Objective:To explore the protective effect of STF-08310,a specific inhibitor of inositol-requiring enzyme 1 endoribonuclease(IRE1)/spliced X-box binding protein 1(sXBP1)on liver ischemia-reperfusion(IR)injury and the possible mechanisms. Methods:Thirty C57 BL/6 mice were randomly divided into 3 groups(10 in each group):sham operation group(sham group),hepatic ischemia-reperfusion group(IR group),and STF-083010 pretreatment plus hepatic ischemia-reperfusion group(IR+STF-083010 group). Levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum were detected by enzyme-linked immunosorbent assay(ELISA). The histological damage of liver and the apoptosis of hepatocytes were evaluated by hematoxylin-eosin(HE)and TUNEL staining. The expression of interleukin(IL)-6,tumor necrosis factor(TNF)-α,and IL-1β mRNA were examined by RT-qPCR. sXBP1 and CHOP proteins in liver tissues were determined by immunohistochemistry and Western blot.Results:Compared to IR group,plasma ALT and AST levels in STF-083010+IR group were significantly lower(P< 0.01). Liver tissues in STF-083010+IR group were more slightly damaged than those in IR group(P< 0.01). The mRNA levels of IL-6,TNF-α and IL-1β in IR+STF-083010 group and the protein levels of sXBP1 and CHOP were significantly lower than those of IR group(P< 0.01).Conclusion:Pretreatment of STF-083010 can alleviate liver IR injury by inhibiting sXBP1/CHOP signal pathway.
作者
詹峰
蒋超
张楷
龚伟达
王荇
张云
ZHAN Feng;JIANG Chao;ZHANG Kai;GONG Weida;WANG Xing;ZHANG Yun(Department of Hepatobiliary and Laparoscopic Surgery,the Affiliated Yixing Hospital of Jiangsu University,Yixing 214200,China)
出处
《南京医科大学学报（自然科学版）》
CAS
CSCD
北大核心
2021年第10期1447-1452,共6页
Journal of Nanjing Medical University(Natural Sciences)
基金
无锡市卫生健康委科研项目(青年项目)(Q202027)
宜兴市科技创新(社会发展类)专项资金项目(2019SF04)。
作者简介
通信作者:张云,E⁃mail:staff784@yxph.com。
