Page 29 - 第10期

第41卷第10期 南京医科大学学报（自然科学版）
2021年10月 Journal of Nanjing Medical University（Natural Sciences） ·1447 ·

·基础医学·

肌醇依赖酶 1 内切酶活性抑制剂 STF⁃083010 对肝脏缺血再灌

注损伤的保护作用

詹 峰，蒋 超，张 楷，龚伟达，王 荇，张 云 *

江苏大学附属宜兴医院肝胆腹腔镜外科，江苏 无锡 214200

［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⁃1β mRNA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/EBP⁃
homologous 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⁃1β mRNA 水平及 sXBP1、CHOP 蛋白水平明显降低
（P＜0.01）。结论：STF⁃083010预处理可通过抑制sXBP1/CHOP通路减轻肝脏缺血再灌注损伤。
［关键词］ STF⁃083010；缺血再灌注损伤；肝脏；内质网应激
［中图分类号］ R364.1 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）10⁃1447⁃06
doi：10.7655/NYDXBNS20211004

Protective mechanism of inositol⁃requiring enzyme 1 endoribonuclease specific inhibitor
STF⁃083010 against liver ischemia⁃reperfusion injury

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

［Abstract］ 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 C57BL/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.
［Key words］ STF⁃083010；ischemia⁃reperfusion injury；liver；ER stress
［J Nanjing Med Univ，2021，41（10）：1447⁃1452］
［基金项目］ 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）
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通信作者（Corresponding author），E⁃mail：staff784@yxph.com