基于JAK2/STAT3和JNK信号通路研究蒲公英甾醇对急性重型肝炎的保护作用  

Protective Effect of Taraxasterol on Acute Severe Hepatitis Based on JAK2/STAT3/JNK Signaling Pathway

作　　者：尹奕凡 李赫伟[1] 陶田秀 徐宝灵 张可锋[1,3] 高雅 YIN Yifan;LI Hewei;TAO Tianxu;XU Baoling;ZHANG Kefeng;AO Ya(Pharmacology Laboratory of Prevention and Treatment of High Incidence of Disease,Guilin Medical University,Guilin 541199;The Second Afiliated Hospital of Guilin Medical University,Guili1n541199;Guangxi Key Laboratory of Diabetic Systems Medicine,Guil0in 541100)

机构地区：[1]桂林医学院高发病防治药理学重点实验室,桂林541199 [2]桂林医学院第二附属医院,桂林541199 [3]广西糖尿病系统医学重点实验室,桂林541100

出　　处：《中药药理与临床》2023年第8期57-61,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:82060811);广西研究生教育创新计划项目(编号:YCSW2021247)。

摘　　要：目的:研究蒲公英甾醇对急性重型肝炎小鼠的肝保护作用并基于酪氨酸激酶2/转录因子3/c-Jun氨基末端激酶(JAK2/STAT3/JNK)信号通路探讨其作用机制。方法:60只昆明小鼠随机分为正常对照组、模型对照组、水飞蓟素120 mg/kg组、蒲公英甾醇2.5、5、10 mg/kg组,每组10只。各组灌胃相应药物或生理盐水,1次/d,连续15 d,末次药后2 h后,正常对照组小鼠腹腔注射生理盐水,其余各组小鼠腹腔注射D-氨基半乳糖(D-GalN)500 mg/kg和脂多糖(LPS)10μg/kg建立急性重型肝炎模型,腹腔注射体积为4 mL/kg,禁食不禁水6 h后,取血并收集小鼠肝脏。生化法检测小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)以及肝组织中丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)以及总超氧化物歧化酶(T-SOD)含量或活力;ELISA法检测肝组织中白介素-6(IL-6)、肿瘤坏死因子(TNF-α)、IL-1β含量;HE染色观察肝组织的病理变化程度;Western blot法检测细胞因子信号转导抑制因子3(SOCS3)、转录因子3(STAT3)、c-Jun氨基末端激酶(JNK)蛋白表达。结果:与正常对照组比较,模型对照组小鼠血清中ALT、AST活力和肝组织中MDA、TNF-α、IL-6、IL-1β含量显著升高,T-SOD和GSH-Px的活力显著降低(P<0.01),肝组织p-STAT3和p-JNK蛋白表达显著上调(P<0.01);与模型对照组相比,蒲公英甾醇和水飞蓟素可不同程度地改善小鼠急性重型肝炎发展进程,其中蒲公英甾醇10 mg/kg可显著降低小鼠血清中的ALT、AST活力以及肝组织中MDA、TNF-α、IL-6、IL-1β的含量(P<0.01),提高肝组织中T-SOD和GSH-Px的活力,下调p-STAT3、p-JNK蛋白表达,显著上调SOCS3的蛋白表达(P<0.01)。结论:蒲公英甾醇对D-GalN/LPS致急性重型肝炎小鼠肝脏具有保护作用,其保肝机制可能通过上调SOCS3从而调控JAK2/STAT3及JNK信号通路,进而抑制炎症反应相关。Objective:To investigate the hepatoprotective effect and mechanism of taraxasterol in mice with acute severe hepatitis based on the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)/c-Jun N-terminal kinase(JNK)signaling pathway.Methods:Sixty Kunming mice were randomly divided into a normal control group,a model control group,silymarin(120 mg/kg)group,and taraxasterol(2.5,5,and 10 mg/kg)groups,with 10 mice in each group.The corresponding drugs or physiological saline were administered orally once daily for 15 consecutive days.Two hours after the final administration,mice in the normal control group received an intraperitoneal injection of physiological saline,while mice in the other groups received an intraperitoneal injection of D-galactosamine(D-GalN)at 500 mg/kg and lipopolysaccharide(LPS)at 10μg/kg to establish an acute severe hepatitis model.The injection volume was 4 mL/kg.After a 6-hour fasting period with free access to water,blood samples were collected and mouse livers were harvested.Biochemical assays were performed to measure the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in mouse serum,and malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and total superoxide dismutase(T-SOD)in liver tissues.ELISA was used to determine the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and IL-1βin liver tissues.Histopathological changes in the liver were observed through HE staining.Western blot analysis was conducted to assess the protein expression of suppressor of cytokine signaling 3(SOCS3),STAT3,and JNK.Results:Compared with the normal control group,mice in the model control group showed significantly increased activity of ALT and AST in serum,elevated levels of MDA,TNF-α,IL-6,and IL-1βin liver tissues,decreased activity of T-SOD and CSH-Px(P<0.01),and upregulated protein expression of p-STAT3 and p-JNK in livertissues(P<0.O1).Compared with the model control group,taraxasterol and silymarin improved the progression of acute severe hepa

关 键 词：蒲公英甾醇 急性重型肝炎 D-氨基半乳糖/脂多糖 抗炎 酪氨酸激酶2/转录因子3/c-Jun氨基末端激酶信号通路 

分 类 号：R285.5[医药卫生—中药学]