木犀草素对大鼠自身免疫性肝炎的肝功能保护作用及其机制研究  

Protective effect of luteolin on liver function in rats with autoimmune hepatitis and its mechanism

作　　者：赖玺杰[1,2] 林列威 刘洪亮 李红山 LAI Xijie;LIN Liwei;LIU Hongliang;LI Hongshan(Department of Liver Disease,Ningbo No.2 Hospital,Ningbo 315010,China;Department of Infectious Diseases,Ningbo Fenghua District People's Hospital&Medical Community General Hospital,Ningbo 315500,China)

机构地区：[1]宁波市第二医院肝病科,315010 [2]宁波市奉化区人民医院(宁波市奉化区人民医院医共体总院)感染科,315500

出　　处：《免疫学杂志》2024年第5期452-457,共6页Immunological Journal

基　　金：浙江省自然科学基金(LQ22H290001);宁波市中医医学重点学科建设计划中西医结合肝病学(2022-Z01)。

摘　　要：目的观察木犀草素(luteolin,LT)对自身免疫性肝炎(autoimmune hepatitis,AIH)大鼠肝纤维化的保护作用,并探讨可能机制。方法62只大鼠随机选取52只尾静脉注射伴刀豆球蛋白A(Con A)生理盐水溶液建立AIH模型,随机分为AIH模型组(AIH组,10只),LT低、中、高剂量组(LT L组、LT M组、LT H组,各10只)及泼尼松龙组(PSL组,10只),其余10只尾静脉注射等体积生理盐水,设为对照组(CT组)。LT L、M、H组腹腔注射LT生理盐水溶液(LT剂量分别为5、25、50 mg/kg),PSL组腹腔注射PSL生理盐水溶液(PSL剂量为10.0 mg/kg),CT组、AIH组腹腔注射等体积生理盐水。每日2次,持续7 d。干预完成后次日检测各组肝功能指标、外周血淋巴细胞亚群、肝组织羟脯氨酸含量;Masson染色观察肝组织纤维化情况;免疫印迹法检测肝组织激活核转录因子κB(NF-κB)、p-NF-κB、核因子抑制蛋白(IκBα)、p-IκBα蛋白表达量。结果与CT组比较,AIH组大鼠血清谷丙转氨酶(ALT)、总胆红素(TBIL)水平,CD4^(+)T淋巴细胞占比、CD4^(+)/CD8^(+)比值、肝组织羟脯氨酸水平均升高(P<0.05),白蛋白(ALB)水平、CD8^(+)T淋巴细胞占比均降低(P<0.05);与AIH组比较,LT各剂量组血清ALT、TBIL水平,CD4^(+)T淋巴细胞占比、CD4^(+)/CD8^(+)比值、肝组织羟脯氨酸水平均降低(P<0.05),ALB水平、CD8^(+)T淋巴细胞占比均升高(P<0.05),且表现为剂量依赖(P<0.05);LT H组、PSL组各指标比较,差异均无统计学意义(P>0.05)。Masson染色结果显示,LT各剂量组大鼠的肝纤维化程度较AIH组减轻,且表现为剂量依赖,PSL组显示出类似LT H组的纤维化抑制效果。与CT组比较,AIH组大鼠肝组织p-NF-κB p65/NF-κB p65、p-IκBα/IκBα均升高(P<0.05);与AIH组比较,LT各剂量组肝组织p-NF-κB p65/NF-κB p65、p-IκBα/IκBα均降低(P<0.05),且表现为剂量依赖(P<0.05);LT H组、PSL组肝组织p-NF-κB p65/NF-κB p65、p-IκBα/IκBα比较,差异均无统计学意义(P>0.05)。结论LT可改善To assess the protective effects of luteolin(LT)on liver fibrosis in rats with autoimmune hepatitis(AIH)and to explore the underlying mechanisms,total of 62 rats were recruited and randomly divided into normal control group(CT),AIH model group(AIH),LT low-dose group(LT L),LT medium-dose group(LT M),LT high-dose group(LT H)and prednisolone group(PSL),with 10 rats in each group.The rat in CT group were injected with an equivalent volume of physiological saline via the tail vein,when the rat in the other groups were received tail vein injection of concanavalin A(Con A)dissolved in physiological saline to induce the AIH model.Then,the rat in LT L,M,and H groups were administered intraperitoneal injections of LT dissolved in physiological saline(at doses of 5,25,and 50 mg/kg,respectively),and the rat in the PSL group received intraperitoneal injections of PSL dissolved in physiological saline(at a dose of 10.0 mg/kg),while the rat in the CT and AIH groups received equivalent volumes of physiological saline intraperitoneally.All treatments were administered twice daily for 7 consecutive days.The day after the last treatment,liver function indices,peripheral blood lymphocyte subsets,and hepatic hydroxyproline content were measured.Furthermore,Masson staining was used to assess the liver fibrosis was assessed using,and Western blot analysis was performed to detect the expression levels of activated nuclear factorκB(NF-κB),phosphorylated NF-κB(p-NF-κB),inhibitor of nuclear factorκBα(IκBα),and phosphorylated IκBα(p-IκBα)proteins in liver tissue.Compared to the CT group,the AIH group exhibited significantly higher serum levels of alanine aminotransferase(ALT),total bilirubin(TBIL),CD4^(+)T lymphocyte ratio,CD4^(+)/CD8^(+)ratio,and hepatic hydroxyproline content(P<0.05),while albumin(ALB)levels and the CD8^(+)T lymphocyte ratio were significantly lower(P<0.05).LT in all doses could reverse these changes mentioned above in AIH rats in a dose-dependent manner(P<0.05),and no significant differences were observed bet

关 键 词：木犀草素 自身免疫性肝炎 肝纤维化 激活核转录因子κB 

分 类 号：R575.1[医药卫生—消化系统]