摘要
目的:研究槲芪方加减对肝癌化疗栓塞术后大鼠一氧化氮合酶(iNOS)、血管内皮生长因子(VEGF)、乏氧及免疫功能的影响。方法:50只大鼠中随机抽取12只作为健康组进行对照,37只大鼠建立肝癌模型。建模过程中意外死亡1只大鼠,剩余36只大鼠建模成功,随机分为模型组、肝动脉化疗栓塞术组以及联合组,每组12只。肝动脉化疗栓塞术组给予肝动脉化疗栓塞术(TACE)治疗;联合组在肝动脉化疗栓塞术组基础上给予模型大鼠27 ml/kg槲芪方灌胃,2次/d,共24周。运用全自动生化分析仪检测各组大鼠肝功能指标水平,流式细胞仪检测各组大鼠免疫功能指标水平,苏木精-伊红(HE)染色观察各组大鼠肝组织病理变化,原位末端标记法(TUNEL)检测各组大鼠肝癌细胞凋亡,免疫印迹检测各组大鼠VEGF、iNOS、缺氧诱导因子1α(HIF-1α)蛋白表达。结果:与健康组比较,模型组丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)水平均升高(P<0.05),与模型组比较,肝动脉化疗栓塞术组ALT、AST、ALP水平均降低(P<0.05),肝动脉化疗栓塞术组ALT、AST、ALP水平均高于联合组(P<0.05)。与健康组比较,模型组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)降低,CD8^(+)升高(P<0.05),模型组与联合组比较差异无统计学意义(P>0.05),与模型组及联合组比较,肝动脉化疗栓塞术组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)降低,CD8^(+)升高(P<0.05)。与健康组比较,模型组细胞凋亡率升高(P<0.05),与模型组比较,肝动脉化疗栓塞术组细胞凋亡率降低(P<0.05),肝动脉化疗栓塞术组细胞凋亡率低于联合组(P<0.05)。与健康组比较,模型组VEGF、iNOS、HIF-1α表达均升高(P<0.05),与模型组比较,肝动脉化疗栓塞术组VEGF、iNOS、HIF-1α表达均升高(P<0.05),与肝动脉化疗栓塞术组比较,联合组VEGF、iNOS、HIF-1α表达均降低(P<0.05)。结论:槲芪方加减可提高肝癌TACE术后大鼠的免疫功能,通过抑制肝癌大鼠乏氧微环境中HIF-1α、iNOS及VEGF水平,改善乏氧微环境,促进肿瘤细胞凋亡。
Objective:To investigate the effects of Huqi formula plus-minus on inducible nitric oxide synthase(iNOS),vascular endothelial growth factor(VEGF),hypoxia,and immune function in rats with liver cancer after chemotherapy embolization.Methods:Fifty rats were randomly selected,with 12 rats used as the healthy control group,and 37 rats were used to establish a liver cancer model.During the modeling process,one rat died unexpectedly,leaving 36 rats for successful modeling.They were randomly divided into the model group,the hepatic artery chemoembolization group,and the combination group,with 12 rats in each group.The hepatic artery chemoembolization group received hepatic artery chemoembolization(TACE) treatment;the combination group received oral administration of 27 ml/kg of Huqi formula twice a day for a total of 24 weeks on the basis of the hepatic artery chemoembolization group.The levels of liver function indicators in each group of rats were detected using an automatic biochemical analyzer,and the levels of immune function indicators were detected using flow cytometry.The pathological changes of liver tissues in each group of rats were observed by hematoxylin-eosin(HE) staining,and the apoptosis of liver cancer cells in each group of rats was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) method.The protein expression of VEGF,iNOS,and hypoxia-inducible factor 1α(HIF-1α) in each group of rats was detected by immunoblotting.Results:Compared with the healthy control group,the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP) in the model group increased(P<0.05).Compared with the model group,the levels of ALT,AST,and ALP in the hepatic artery chemoembolization group were decreased(P<0.05),but the levels in the hepatic artery chemoembolization group were higher than those in the combination group(P<0.05).Compared with the healthy control group,the levels of CD3^(+),CD4^(+),and CD4^(+)/CD8^(+) in the model group decreased,while the level of CD8^(+) increased(P<0.05).There was no statistical difference in these indicators between the model group and the combination group(P>0.05).Compared with the model group,the levels of CD3^(+),CD4^(+),and CD4^(+)/CD8^(+) in the hepatic artery chemoembolization group decreased,while the level of CD8^(+) increased(P<0.05).Compared with the healthy control group,the apoptosis rate in the model group were increased(P<0.05).Compared with the model group,the apoptosis rate in the hepatic artery chemoembolization group decreased(P<0.05),but the apoptosis rate in the hepatic artery chemoembolization group was lower than that in the combination group(P<0.05).Compared with the healthy control group,the expression of VEGF,iNOS,and HIF-1α in the model group were increased(P<0.05).Compared with the model group,the expression of VEGF,iNOS,and HIF-1α in the hepatic artery chemoembolization group were increased(P<0.05),while the expression in the combination group was decreased(P<0.05).Conclusion:Huqi formula can improve the immune function of rats after TACE operation,improve the hypoxic microenvironment and promote tumor cell apoptosis by inhibiting the levels of HIF-1α,iNOS and VEGF in hypoxic microenvironment of rats.
作者
孔庆旭
陈桂云
陈自力
李俊
KONG Qingxu;CHEN Guiyun;CHEN Zili;LI Jun(Zhongxiang Hospital of Traditional Chinese Medicine,Zhongxiang 431900,China)
出处
《陕西中医》
CAS
2024年第2期181-186,共6页
Shaanxi Journal of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(81473268)
贵州医科大学国家自然科学基金培育项目(19NSP012)。
关键词
肝癌
肝癌化疗栓塞术
槲芪方
大鼠
一氧化氮合酶
血管内皮生长因子
乏氧
免疫功能
Liver cancer
Chemoembolization for liver cancer
Huqi formula
Rats
Inducible nitric oxide synthase
Vascular epidermal growth factor
Anoxia
Immune function
