基于NLRP NLRP3信号通路探讨黑果小檗提取物对模型小鼠肝纤维化的影响  

Effect of Berberis Heteropoda Extract on Liver Fibrosis in Model Mice Based on the NLRP3 Signaling Pathway

作　　者：李渊[1] 顾伟萍[1] 孙吉祥[1] 毕慧 刘菁[1] LI Yuan;GU Weiping;SUN Jixiang;BI Hui;LIU Jing(Xinjiang Uygur Autonomous Region People's Hospital,Urumqi,Xinjiang,China 830011)

机构地区：[1]新疆维吾尔自治区人民医院,新疆乌鲁木齐830011

出　　处：《中国药业》2025年第9期58-62,共5页China Pharmaceuticals

基　　金：新疆维吾尔自治区自然科学基金[2021D01C177]。

摘　　要：目的基于核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3(NLRP3)信号通路探讨黑果小檗提取物(BHSTA)对模型小鼠肝纤维化的影响。方法将35只雄性小鼠随机分为正常对照组(A组,等量蒸馏水),模型对照组(B组,等量蒸馏水),秋水仙碱组(C组,2 mg/kg秋水仙碱),BHSTA低、高剂量组(D_(1)组、D_(2)组,10,40 mg/mLBHSTA),各7只。B组、C组、D_(1)组、D_(2)组小鼠均腹腔注射3μL/g四氯化碳(CCl4)油剂(CCl4∶橄榄油=1∶4,V/V)4周,每周2次,复制肝纤维化小鼠模型,A组小鼠仅腹腔注射3μL/g CCl44周,每周2次。之后各组小鼠每天灌胃1次相应药物,连续4周。观察小鼠的一般情况(包括精神状态、饮水量、饮食量、体质量、活动量);肝脏组织经苏木精-伊红(HE)染色,观察肝脏病理形态变化;检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平和NLRP3、凋亡相关微粒蛋白(ASC)、白细胞介素1β(IL-1β)、胱天蛋白酶1(caspase-1)的蛋白表达水平。结果与B组比较,D_(1)组、D_(2)组小鼠的精神状态尚可,饮食量、饮水量尚可,体质量增加,活动量正常;肝脏细胞形态趋于正常,炎性细胞浸润减少;ALT,AST水平及NLRP3,ASC,IL-1β,caspase-1蛋白表达水平均显著降低(P<0.05)。结论BHSTA可有效抑制肝纤维化模型小鼠肝星状细胞的活化,改善肝脏功能,减轻炎性反应,其作用机制可能与抑制NLRP3信号通路相关。Objective To investigate the effect of Berberis heteropoda extract(BHSTA)on liver fibrosis in mice model based on the NLRP3 signaling pathway.Methods A total of 35 male mice were randomly divided into the normal control group(group A,equal volume of distilled water),the model control group(group B,equal volume of distilled water),the colchicine group(group C,2 mg/kg colchicine),and BHSTA low-and high-dose groups(groups D_(1),D_(2);10,40 mg/mL BHSTA),with seven mice in each group.Mice in groups B,C,D_(1),and D_(2) were intraperitoneally injected with 3µL/g carbon tetrachloride(CCl4)oil(CCl4∶olive oil=1∶4,V/V)twice a week for four weeks to replicate mice model with liver fibrosis.Mice in group A were only intraperitoneally injected with 3µL/g CCl4 twice a week for four weeks.Afterwards,mice in each group were orally administered with the corresponding drug once a day for four weeks.The general condition of mice(mental state,water intake,diet,body weight,and activity level)was observed.The liver tissue was stained with hematoxylin-eosin(HE)to observe pathological changes in the liver.The levels of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST),as well as the expression levels of NLRP3,apoptosis-related microglobulin(ASC),interleukin-1β(IL-1β),and caspase-1 proteins were detected.Results Compared with those in group B,the mental state,diet,and water intake of mice in groups D_(1) and D_(2) were still acceptable,their body weight increased,and their activities were normal;the morphology of liver cells tended to be normal,and the infiltration of inflammatory cells decreased in groups D_(1) and D_(2);the levels of ALT and AST,as well as the expression levels of NLRP3,ASC,IL-1β,and caspase-1 protein in groups D_(1) and D_(2) significantly decreased(P<0.05).Conclusion BHSTA can effectively inhibit the activation of hepatic stellate cells in model mice with liver fibrosis,improve liver function,and alleviate inflammatory reactions.Its mechanism may be related to the inhibition of the NLRP3

关 键 词：黑果小檗提取物 肝纤维化 核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3 肝星状细胞 炎性反应 作用机制 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]