IL-22对大鼠肝脏缺血再灌注损伤的影响及相关机制

Effects of IL-22 on hepatic ischemia-reperfusion injury and related mechanism in SD rats

目的探究白细胞介素22(IL-22)对大鼠肝脏缺血再灌注损伤(IRI)的作用及相关机制。方法将18只健康雄性无特定病原体SD大鼠(7~8周龄,250 g左右)随机分为三组:假手术组(Sham)、肝脏缺血再灌注组(IRI)、IL-22预处理组(IL-22+IRI)。构建70%大鼠肝脏IRI模型,IL-22+IRI组术前1 h腹腔注射重组IL-22(50 mg/kg),Sham组、IRI组术前1 h注射等体积生理盐水。缺血1 h再灌注6 h后取血及肝脏组织检测血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平,检测肝组织超氧化物歧化酶(SOD)、丙二醛(MDA)水平,Western blot法检测信号转导和转录激活因子3(STAT3)、磷酸化STAT3(p-STAT3)、核因子E2相关因子2(Nrf2)和血红素加氧酶1(HO-1)的表达。结果与Sham组比较,IRI组和IL-22+IRI组血清AST[(1923.50±92.63)U/L、(1004.25±65.05)U/L]和ALT[(1172.51±180.31)U/L、(583.50±164.75)U/L]水平升高(AST:F=293.62;ALT:F=30.33),肝组织MDA[(1.72±0.12)μmol/mg、(0.98±0.05)μmol/mg]水平较Sham组(0.58±0.14)μmol/mg升高(F=186.73),p-STAT3、Nrf2、HO-1表达增加,IRI组SOD水平(28.51±3.85)U/mg较Sham组(70.25±5.64)U/mg降低(F=203.41),差异均有统计学意义(均P<0.05);与IRI组相比,IL-22+IRI组大鼠血清AST和ALT水平下降,肝组织SOD活性增加,MDA水平下降,p-STAT3、Nrf2、HO-1表达增加,差异均有统计学意义(均P<0.05)。结论IL-22可减轻大鼠肝脏IRI,其机制可能与激活STAT3以及Nrf2/HO-1信号通路和抑制氧化应激有关。

Objective To investigate the protective effect of IL-22 on rat liver ischemia reperfusion injury(IRI)and the potential mechanisms.Methods Eighteen male specific pathogen free SD rats(7-8 weeks,about 250g)were randomly divided into three groups:Sham group(Sham),hepatic ischemia reperfusion(IRI)and IL-22 preconditioning group(IL-22+IRI),respectively.The liver IRI model of 70%rats was established.The IL-22+IRI group was intraperitoneally injected with rcIL-22(50 mg/kg)1 hour before surgery,and the Sham group and IRI group were injected with the same dose of normal saline 1 hour before surgery.After 1 h ischemia and 6 h reperfusion,blood was collected from the abdominal aorta,then liver tissue,serum aspartate transaminase(AST)and alanine aminotransfease(ALT)levels were measured.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tissue were detected.The expression of signal transducer and activator of transcription 3(STAT3),p-STAT3,nuclear factor erythorid-2 related factor 2(Nrf2)and heme oxygenase 1(HO-1)were detected by Western blot.Results Compared with Sham group,serum AST[(1923.50±92.63)U/L,(1004.25±65.05)U/L]and ALT[(1172.51±180.31)U/L,(583.50±164.75)U/L]levels were increased in IRI group and IL-22+IRI group(AST:F=293.62;ALT:F=30.33,P<0.05).The levels of MDA in IRI group and IL-22+IRI group[(1.72±0.12)μmol/mg,(0.98±0.05)μmol/mg]in liver tissue were higher than those in Sham group(0.58±0.14)μmol/mg protein(F=186.73,P<0.05),and the expression of p-STAT3,Nrf2 and HO-1 was increased.SOD level in IRI group(28.51±3.85)U/mg was lower than that in Sham group(70.25±5.64)U/mg protein(F=203.41,P<0.05).Compared with IRI group,serum AST and ALT levels in IL-22+IRI group were decreased,SOD activity in liver tissue was increased,MDA level was decreased,and p-STAT3,Nrf2 and HO-1 expression was increased(all P<0.05).Conclusion IL-22 could alleviate liver IRI in rats,and the mechanism may be related to the activation of STAT3 and Nrf2/HO-1 signaling pathway and anti-oxidative stress.