SIRT1-NLRP3轴介导的细胞焦亡在瑞芬太尼抗肝脏缺血-再灌注损伤中的作用研究

Study on SIRT1-NLRP3 axis-mediated pyroptosis in the role of remifentanil against liver ischemia-reperfusion injury

    摘要
  • 摘要:
    目的  探讨沉默信息调节因子1（SIRT1）-NOD样受体蛋白3（NLRP3）轴在瑞芬太尼抗大鼠肝脏缺血-再灌注损伤（IRI）中的作用及机制。
    方法  将SD大鼠随机分为假手术组（sham组）、IRI组、IRI+瑞芬太尼预处理组（IRI+RPC组）、IRI+SIRT1抑制剂EX-527组（IRI+EX-527组）和IRI+RPC+EX-527组，每组8只。检测各组大鼠血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）、白细胞介素（IL）-1β和IL-18水平；观察肝组织病理；检测大鼠肝细胞凋亡率；检测大鼠肝组织SIRT1、NLRP3、裂解的半胱氨酸天冬氨酸蛋白酶（Cleaved Caspase-1）和Gasdermin D（GSDMD）蛋白表达。
    结果  与sham组比较，IRI组大鼠肝组织病理评分及肝细胞凋亡率升高，血清ALT、AST、LDH、IL-1β、IL-18水平升高，肝组织SIRT1蛋白相对表达量降低，NLRP3、Cleaved Caspase-1、GSDMD蛋白相对表达量升高（均为P<0.05）。与IRI组比较，IRI+RPC组肝组织病理评分及肝细胞凋亡率下降，血清ALT、AST、LDH、IL-1β、IL-18水平降低，肝组织SIRT1蛋白相对表达量升高，NLRP3、Cleaved Caspase-1、GSDMD蛋白相对表达量降低；IRI+EX-527组肝组织病理评分及肝细胞凋亡率升高，ALT、AST、LDH、IL-1β、IL-18水平升高，肝组织SIRT1蛋白相对表达量下降，NLRP3、Cleaved Caspase-1、GSDMD蛋白相对表达量升高（均为P<0.05）。与IRI+RPC组比较，IRI+RPC+EX-527组肝组织病理评分及肝细胞凋亡率升高，ALT、AST、LDH、IL-1β、IL-18水平升高，肝组织SIRT1蛋白相对表达量下降，NLRP3、Cleaved Caspase-1、GSDMD蛋白相对表达量升高（均为P<0.05）。
    结论  SIRT1可通过抑制NLRP3介导的细胞焦亡参与调节瑞芬太尼抗大鼠肝脏IRI。

     

    Abstract:
    Objective To investigate the role and mechanism of silent information regulator 1 (SIRT1)-NOD-like receptor protein 3 (NLRP3) axis in the effect of remifentanil against ischemia-reperfusion injury (IRI) in rat livers.
    Methods SD rats were randomly divided into sham operation group (sham group), IRI group, IRI+remifentanil pretreatment group (IRI+RPC group), IRI+SIRT1 inhibitor EX-527 group (IRI+EX-527 group) and IRI+RPC+EX-527 group, with 8 rats in each group. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), interleukin (IL)-1β and IL-18 of rats in each group were detected. The liver tissue pathology was observed. The apoptosis rate of hepatocytes in rats was detected. The expressions of SIRT1, NLRP3, cleaved cysteinyl aspartate specific proteinase-1 (Cleaved Caspase-1) and Gasdermin D (GSDMD) proteins in rat liver tissue were detected.
    Results Compared with the sham group, the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI group were increased, the serum ALT, AST, LDH, IL-1β, and IL-18 levels were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05). Compared with the IRI group, the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+RPC group were decreased, the serum ALT, AST, LDH, IL-1β, and IL-18 levels were decreased, the relative expression of SIRT1 protein in liver tissue was increased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were decreased; the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+EX-527 group were increased, the ALT, AST, LDH, IL-1β, and IL-18 levels were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05). Compared with the IRI+RPC group, the liver tissue pathological score and hepatocyte apoptosis rate in the IRI+RPC+EX-527 group were increased, the levels of ALT, AST, LDH, IL-1β, and IL-18 were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05).
    Conclusions SIRT1 may participate in the regulation of remifentanil against rat liver IRI by inhibiting NLRP3 mediated cell pyroptosis.

     

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