制萎扶胃丸对胃癌前病变模型大鼠的干预作用研究  

Research on the intervention of Zhiwei Fuwei pills on rats with precancerous lesions of gastric cancer

作　　者：豆鹏程 袁学玲 宋瑞平 封壮壮 姚柳伊[2] 陈心怡 王晓龙 左娇娇 舒劲[2] DOU Peng-cheng;YUAN Xue-ling;SONG Rui-ping;FENG Zhuang-zhuang;YAO Liu-yi;CHEN Xin-yi;WANG Xiao-long;ZUO Jiao-jiao;SHU Jin(Clinical College of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730030,Gansu Province,China;Spleen and Stomach Disease Diagnosis and Treatment Center,Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,Gansu Province,China;Central Laboratory,Gansu Academy of Traditional Chinese Medicine,Lanzhou 730050,Gansu Province,China)

机构地区：[1]甘肃中医药大学中医临床学院,甘肃兰州730030 [2]甘肃省中医院脾胃病诊疗中心,甘肃兰州730050 [3]甘肃省中医药研究院中心实验室,甘肃兰州730050

出　　处：《中国临床药理学杂志》2024年第23期3429-3433,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(82060860);甘肃省自然科学基金资助项目(21JR7RA588)。

摘　　要：目的基于缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路探究制萎扶胃丸对胃癌前病变(PLGC)模型大鼠的干预作用,及其作用机制。方法通过N-甲基-N′-硝基-N-亚硝基胍联合氨水自由饮用、饥饱失常、乙醇灌胃、雷尼替丁饲料喂养的复合造模法构建PLGC模型大鼠,并随机分为模型组、对照组及高、中、低剂量实验组,每组8只;另取8只健康大鼠设为空白组。高、中、低剂量实验组分别灌胃给予1.67、0.84、0.42 g·kg^(-1)制萎扶胃丸溶液,对照组灌胃给予2.00×10^(-3)g·kg^(-1)叶酸溶液,空白组和模型组均灌胃给予等量0.9%NaCl,每日1次,共4周。用透射电子显微镜检测胃组织微血管结构变化,用蛋白质印迹法检测HIF-1α、VEGF、血管内皮生长因子受体-2(VEGFR-2)和血管生成素-2(Ang-2)蛋白的表达水平。结果相较于模型组,低、中、高剂量实验组大鼠胃组织微血管结构异常现象出现一定程度的改善,其中以高剂量实验组效果最为明显。高、中剂量实验组和对照组、模型组、空白组的HIF-1α蛋白相对表达水平分别为0.43±0.03、0.66±0.04、0.77±0.01、0.80±0.02和0.37±0.02,VEGF蛋白相对表达水平分别为0.97±0.06、1.21±0.06、1.51±0.07、1.54±0.05和0.88±0.02,VEGFR-2蛋白相对表达水平分别为1.03±0.06、1.18±0.04、1.37±0.05、1.45±0.02和0.70±0.02,Ang-2蛋白相对表达水平分别为0.51±0.03、0.61±0.02、0.71±0.01、0.78±0.03和0.34±0.01。高、中剂量实验组的上述指标与模型组相比,在统计学上差异均有统计学意义(均P<0.01)。结论制萎扶胃丸可能通过抑制HIF-1α/VEGF信号通路异常激活,改善缺氧微环境,减少血管生成,从而有效干预PLGC进展。Objective To explore the intervention effect and mechanism of Zhiwei Fuwei pills on precancerous lesions of gastric cancer(PLGC)model rats based on hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods PLGC model rats were established by the combination of N-methyl-N′-nitro-N-nitrosoguanidine and ammonia drinking,hunger and satiation disorder,ethanol gavage and ranitidine feeding,and were randomly divided into model group,control group and experimental-H,-M,-L groups,with 8 rats in each group.Another 8 healthy rats were selected as blank group.Experimental-H,-M,-L groups were given 1.67,0.84 and 0.42 g·kg^(-1)Zhiwei Fuwei pills solution by intragastric administration,respectively;control group was given 2.00×10^(-3)g·kg^(-1)folic acid solution by intragastric administration;blank group and model group were given 0.9%NaCl by intragastric administration,once a day for 4 weeks.The structural changes of gastric microvessels were detected by transmission electron microscopy,and the expression levels of HIF-1α,VEGF,vascular endothelial growth factor receptor-2(VEGFR-2)and Angiopoietin-2(Ang-2)were detected by western blot.Results Compared with the model group,the abnormality of gastric microvascular structure in experimental-H,-M,-L groups was improved to some extent,and the effect of high dose experimental group was the most obvious.The relative expression levels of HIF-1αprotein in experimental-H,-M groups and control group,model group and blank group were 0.43±0.03,0.66±0.04,0.77±0.01,0.80±0.02 and 0.37±0.02;the relative expression levels of VEGF protein were 0.97±0.06,1.21±0.06,1.51±0.07,1.54±0.05 and 0.88±0.02;the relative expression levels of VEGFR-2 protein were 1.03±0.06,1.18±0.04,1.37±0.05,1.45±0.02 and 0.70±0.02;the relative expression levels of Ang-2 protein were 0.51±0.03,0.61±0.02,0.71±0.01,0.78±0.03 and 0.34±0.01,respectively.Compared with the model group,the above indexes in the experimental-H,-M groups were statistically signif

关 键 词：制萎扶胃丸 胃癌前病变 缺氧诱导因子-1Α 血管内皮生长因子 血管生成素-2 血管内皮生长因子受体-2 

分 类 号：R28[医药卫生—中药学]