鳖甲煎丸经AT1R/VEGF信号通路对肝癌血管生成的影响  

Effect of Biejiajian pill on angiogenesis of liver cancer via AT1R/VEGF signaling pathway

作　　者：李杳瑶[1] 刘华[1] 孙铜林 伍静 孟小莎 伍梦思 苏联军[2] LI Yao-yao;LIU Hua;SUN Tong-lin;WU Jing;MENG Xiao-sha;WU Meng-si;SU Lian-jun(Department of Oncology,The First Hospital of Hunan University of Chinese Medicine,Changsha,Hunan Province 410007,China;Department of Classics Teaching and Research,Hunan University of Chinese Medicine,Changsha,Hunan Province,410208,China)

机构地区：[1]湖南中医药大学第一附属医院肿瘤内科,湖南长沙410007 [2]湖南中医药大学经典教研室,湖南长沙410208

出　　处：《解剖学研究》2023年第6期523-528,共6页Anatomy Research

基　　金：湖南省自然科学基金(2021JJ30523)。

摘　　要：目的 探讨鳖甲煎丸通过AT1R/VEGF信号通路影响肝癌血管生成的相关机制。方法 将40只BALB/c小鼠分为正常组、模型组、阿霉素干预组(DOX组)及鳖甲煎丸干预组(BJJW组),每组各10只。除正常组外,余下3组小鼠均立肝癌HepG2移植瘤模型,造模期间各组给予生理盐水和相应的药物治疗(腹腔注射给药),连续治疗10 d。测量各组小鼠的瘤体体积和瘤体肿瘤,并计算抑瘤率;采用免疫组织化学法检测CD34的表达情况来反映肿瘤组织的微血管密度,并采用Wstern blot法检测各组小鼠肿瘤组织中血管生成相关蛋白——缺氧诱导因子(HIF-1α)、血管内皮生长因子(VEGF)、金属基质蛋白酶-2(MMP-2)和MMP-9水平的表达情况,及血管紧张素Ⅱ1型受体(AT1R)通路相关蛋白含量。结果 与正常对照组相比,模型组与各治疗组小鼠均形成瘤体组织,表示造模成功。其中模型组小鼠肿瘤体积、瘤体肿瘤[分别为(245.32±122.51)cm^(3)、(1.08±0.78)g]均明显大于治疗组[DOX组体积分别为(83.41±12.04)cm^(3)、(110.04±48.07)g;BJJW组分别为(110.04±48.07)cm^(3)、(0.63±0.34)g](P<0.05),肿瘤细胞凋亡率较DOX组和BJJW组明显偏低(P<0.05)。模型组MVD、CD34阳性表达率、VEGF、HIF-1α、MMP-2、MPP-9蛋白含量及AT1R通路相关蛋白含量均较正常对照组明显升高(P<0.05);而DOX组及BJJW组的MVD、CD34阳性表达率、VEGF、HIF-1α、MMP-2、MPP-9蛋白及AT1R通路相关蛋白含量均明显低于模型组(均P<0.05)。结论 鳖甲煎丸可通过抑制肝癌血管的生成来起到抑癌效果,这可能与AT1R/VEGF信号通路被抑制有关。Objective To explore the related mechanism of Biejiajian Pill on angiogenesis of liver cancer through AT1R/VEGF signaling pathway.Methods Forty BALB/c mice were divided into normal control,model,doxorubicin(DOX)and Biejiajian Pill(BJJW)groups,with 10 mice in each group.In addition to the normal group,the remaining three groups of mice were modeled with liver cancer HepG2 xenografts.During the modeling pe⁃riod,each group was given normal saline and corresponding drug therapy(intraperitoneal injection),and continu⁃ous treatment for 10 days.The tumor volume and tumor volume of mice in each group were measured,and the tumor inhibition rate was calculated.The expression of CD34 was detected by immunohistochemistry to reflect the microves⁃sel density of the tumor tissue,and the expression of angiogenesis⁃related proteins——hypoxia⁃inducible factor(HIF⁃1α),vascular endothelial growth factor(VEGF),matrix metalloproteinase⁃2(MMP⁃2)and MMP⁃9,and angioten⁃sin II type 1 receptor(AT1R)pathway⁃related proteins in the tumor tissue of mice in each group were detected by Western blot.Results Compared with the normal control group,tumor bodies were formed in both the model group and each treatment group,indicating the success of modeling.The tumor volume and tumor volume of the model group[(245.32±122.51)cm 3,(1.08±0.78)g]were significantly larger than those of the treatment group[(83.41±12.04)cm^(3) and(110.04±48.07)g];(110.04±48.07)cm^(3) and(0.63±0.34)g in DOX and BJJW group,respectively(P<0.05),and the apoptosis rate of tumor cells was significantly lower than that of DOX group and BJJW group(P<0.05).The MVD,CD34 positive expression rate,VEGF,HIF⁃1α,MMP⁃2,MPP⁃9 protein content and AT1R path⁃way related protein content in the model group were significantly higher than those in the normal control group(P<0.05).The positive expression rates of MVD and CD34,the contents of VEGF,HIF⁃1α,MMP⁃2,MPP⁃9 and AT1R pathway related proteins in the DOX group and BJJW group were significantly low

关 键 词：鳖甲煎丸 肝癌 AT1R/VEGF信号通路 血管生成 

分 类 号：R285.5[医药卫生—中药学]