荷叶碱通过p38MAPK-PPARγ/NF-κB信号通路对肝硬化大鼠的影响  

Effect of nuciferine on liver cirrhosis rats through p38MAPK-PPARγ/NF-κB signaling pathway

作　　者：孟赛[1] 巩林强 李曙晖[1] 邓延梅[1] MENG Sai;GONG Linqiang;LI Shuhui;DENG Yanmei(Department of Gastroenterology,Tengzhou Central People's Hospital,Tengzhou 277599,China)

机构地区：[1]滕州市中心人民医院消化内科,滕州277599

出　　处：《中国免疫学杂志》2025年第3期595-599,共5页Chinese Journal of Immunology

摘　　要：目的:探讨荷叶碱(Nuci)通过p38MAPK-PPARγ/NF-κB信号通路对肝硬化大鼠肝纤维化及炎症反应的影响。方法:随机取6只SD大鼠作为对照(NC)组,其余大鼠200 mg/kg腹腔注射硫代乙酰胺(TAA)诱导肝硬化。造模成功大鼠随机分为Model组、Nuci组(20 mg/kg Nuci)、anisomycin组(5 mg/kg p38MAPK-PPARγ/NF-κB信号通路激活剂anisomycin)、Nuci+anisomycin组(20 mg/kg Nuci+5 mg/kg anisomycin),每组6只,NC组、Model组给予等量生理盐水,1次/d,持续8周。ELISA试剂盒检测血清炎症指标、肝功能指标;HE染色检测肝脏病理变化;Masson染色检测肝组织纤维化;Western blot检测通路相关蛋白水平。结果:NC组细胞结构正常,仅有少量胶原沉积,未见胶原纤维增生现象,肝小叶染色清晰。Model组较NC组肝细胞增大,伴有炎症细胞浸润,且胶原纤维增生现象增加,IL-1β、TNF-α、丙氨酸氨基转移酶(ALT)、IL-6、透明质酸(HA)、天冬氨酸氨基转移酶(AST)、Ⅲ型前胶原(PCⅢ)、总胆红素(TBIL)含量、层粘连蛋白(LN)、胶原容积分数、p-p38MAPK/p38MAPK、p-NF-κB p65/NF-κB p65蛋白水平显著升高(P<0.05),PPARγ蛋白水平显著下调(P<0.05);Nuci治疗改善了肝组织炎症细胞浸润及坏死现象,IL-1β、IL-6、TNF-α、ALT、AST、TBIL、HA、LN和PCⅢ含量、胶原容积分数、p-p38MAPK/p38MAPK、p-NF-κB p65/NF-κB p65蛋白水平显著降低(P<0.05),PPARγ蛋白水平显著升高(P<0.05),而anisomycin组与Nuci组趋势相反;anisomycin消除了Nuci对肝硬化大鼠的治疗作用。结论:Nuci可能通过下调p38MAPK-PPARγ/NF-κB信号通路减轻肝硬化大鼠肝纤维化及炎症反应。Objective:To explore impacts of nuciferine(Nuci)on liver fibrosis and inflammatory reaction in cirrhotic rats through p38MAPK-PPARγ/NF-κB signal pathway.Methods:Six SD rats were randomly selected as control(NC)group,other rats were injected with thioacetamide(TAA)into peritoneum at a dose of 200 mg/kg to induce cirrhosis.Rats successfully modeled were randomly grouped into Model group,Nuci group(20 mg/kg Nuci),anisomycin group(5 mg/kg Nuci p38MAPK-PPARγ/NF-κB signal pathway activator anisomycin),and Nuci+anisomycin group(20 mg/kg Nuci+5 mg/kg anisomycin),with 6 rats in each group.The NC group and the Model group were given the same amount of normal saline once a day for 8 weeks.Serum inflammatory index and liver function index were detected by ELISA kits;HE staining was applied to detect pathological changes of liver;Masson staining was applied to detect liver fibrosis;Western blot was applied to detect pathway related proteins levels.Results:In NC group,cell structure was normal,only a small amount of collagen was deposited,no collagen fiber proliferation was observed,and liver lobule was clearly stained.Compared with NC group,hepatocytes in Model group were enlarged,accompanied by inflammatory cell infiltration,and increased collagen fiber proliferation,IL-1β,TNF-α,alanine aminotransferase(ALT),IL-6,hyaluronic acid(HA),aspartate aminotransferase(AST),typeⅢprocollagen(PCⅢ),total bilirubin(TBIL)content,laminin(LN),collagen volume fraction,p-p38MAPK/p38MAPK,p-NF-κB p65/NF-κB p65 proteins levels were significantly increased(P<0.05),PPARγprotein level was significantly decreased(P<0.05).Nuci treatment improved inflammatory cell infiltration and necrosis in liver tissue,levels of IL-1β,IL-6,TNF-α,ALT,AST,TBIL,HA,LN,PCⅢ,collagen volume fraction,p-p38MAPK/p38MAPK,p-NF-κB p65/NF-κB p65 proteins were significantly decreased(P<0.05),PPARγprotein level was significantly increased(P<0.05),trend of anisomycin group was opposite to that of Nuci group;anisomycin eliminated therapeutic effect of Nuci on cirr

关 键 词：荷叶碱 p38MAPK-PPARγ/NF-κB信号通路 肝硬化 肝纤维化 炎症反应 

分 类 号：Q95-3[生物学—动物学]