基于ANXA1/VEGF通路研究片仔癀对肝癌腹水小鼠的保护作用  

The Liver-protecting Function and Mechanism of Pien Tze Huang on H22 Hepatocellular Carcinoma Ascites Mice Based on ANXA1/VEGF Signaling Pathway

作　　者：林雅[1] 赖文芳[1] 李聪翀 刘毓东 林国清[2] LIN Ya;LAI Wenfang;Li Congchong;Liu Yudong;LIN Guoqing(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350122,China;The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350004,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]福建中医药大学附属人民医院,福建福州350004

出　　处：《福建中医药》2020年第1期37-40,共4页Fujian Journal of Traditional Chinese Medicine

基　　金：福建省自然科学基金面上项目(2016J01775);福建省教育厅科技类一般项目(JAT160243)。

摘　　要：目的观察片仔癀对H22肝癌腹水小鼠的影响,探讨其作用机制。方法通过腹腔注射H22肝癌细胞法制备肝癌腹水小鼠,按体质量随机分为正常组、模型组、片仔癀组(0.2 g/kg)、环磷酰胺组(0.07 g/kg),造模24 h后予相应药液灌胃给药,每日1次,连续给药7 d。实验结束后(7 d后)检测4组小鼠体质量、腹围、腹水量,酶速率法检测血清ALT、AST含量;苏木素-伊红(HE)染色观察小鼠肝组织形态学改变;Western blot法检测膜联蛋白A-1 (ANXA1)、血管内皮生长因子(VEGF)、血管内皮生长因子受体(VEGFR)及核因子κB(NF-κB) p50蛋白表达。结果与正常组比较,模型组小鼠出现明显腹水,肝脏病理提示肝细胞变性坏死,血清ALT、AST含量升高,肝组织ANXA1蛋白表达下降,VEGF、VEGFR、NF-κBp50表达增强(P<0.01或P<0.05);与模型组比较,片仔癀组腹水量明显减少,肝脏病理显示片仔癀组肝小叶结构较为清晰,脂肪空泡减少,肝细胞的液化、退变现象明显减少,血清ALT、AST含量明显下降,肝细胞ANXA1蛋白表达上升,VEGF、VEGFR及NF-KB p50蛋白表达下降(P<0.01或P<0.05)。结论片仔癀可通过调控ANXA1/VEGF通路对H22肝癌腹水小鼠起到保护作用。Objective:To explore the effect of Pien Tze Huang(PZH) on H22 hepatocellular carcinoma(HCC) ascites mice and its mechanism.Methods:Ascites hepatoma mice model were prepared by intraperitoneal injection of H22 HCC,and randomly divided into the normal group,the model group,the PZH group(0.2 g/kg) and the cyclophosphamide group(0.07 g/kg) according to their body weight.The H22 HCC ascites mice were intragastrically administered the respective drugs one time per day,and for consecutive 7 days.At the end of the experiment(7 d later),the body weight,abdominal circumference,ascites volume,ALT and AST level of serum were measured.Observe the pathological section of liver by using HE staining."Western blotting was used to detect the expressions of annexin-A1(ANXA1),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR)and nuclear factor kappa-B(NF-κB) p50.Results:Compared with the normal group,the ascites volume and the serum AST and ALT levels were increased slightly in the model group,the expression of ANXA1 protein decreased,the expression of VEGF,VEGFR,NF-κB p50 protein increased,and the hepatic cells turned partially fatty along with liquidation,regression,or disappearance of cytoplasm.Compared with the model group,PZH could reduce the ascites volume and the serum AST and ALT levels significantly,and the pathological section of liver showed that PZH could improve hepatocytes to a certain extent.The expression of ANXA1 by PZH treatment examined was significantly increased,and VEGF,VEGFR,NF-κB p50 were significantly suppressed.Conclusion:In H22 HCC ascites mice,it suggested that protecting the liver function and regulating ANXA1/VEGF signaling pathway might be the mechanisms by which PZH treats hepatocellular carcinoma.

关 键 词：片仔癀 H22肝癌细胞 腹水 膜联蛋白A1 血管内皮生长因子 NF-κB 小鼠 

分 类 号：R285.5[医药卫生—中药学]