大蒜有效部位组合物对模型大鼠胃癌前病变的疗效和作用机制  

Exploration on Therapeutic Effects and Mechanism of Garlic Effective Parts Composition on Gastric Precancerous Lesions in Model Rats

作　　者：那坤 张立石[2] 王瑞海[2] 柏冬[2] 苗青[2] 孙小鑫[2] 刘丽梅 NA Kun;ZHANG Lishi;WANG Ruihai;BAI Dong;MIAO Qing;LIU Limei(Massage Branch,The Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China;Institute of Basic Theory of Traditional Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100070,China)

机构地区：[1]北京中医药大学第三附属医院推拿科,北京100029 [2]中国中医科学院中医基础理论研究所,北京100700

出　　处：《世界中医药》2021年第19期2891-2898,共8页World Chinese Medicine

基　　金：国家科技重大专项(2009ZX09301-005-035)——基于“大平台”的中药新药探索性研究

摘　　要：目的:研究大蒜油-大蒜皂苷-大蒜多糖组合物治疗胃癌前病变的疗效,阐明该组合物治疗胃癌前病变的作用机制。方法:将大鼠随机分为空白对照组(n=14)和造模组(n=144)。于造模22周时,将造模组大鼠再随机分为6组:模型组(n=24)、大蒜油对照组(n=24)、胃复春对照组(n=24)、组合物高、中、低剂量组(3×24)。连续给药13周后处死。取材后,在光镜下观察胃黏膜的病理学变化。同时,采用电化学发光法检测各组大鼠离心血浆中的3种肿瘤标志物CEA、CA199、CA724的水平。运用Western Blotting和Real-time PCR技术检测胃癌前病变大鼠胃组织中TGF-β1和Smad4的蛋白和mRNA表达情况。结果:1)组合物高剂量(2.38 g/kg)组能够显著地改善胃癌前病变大鼠胃黏膜的病理变化。2)组合物高剂量(2.38 g/kg)组能够明显降低胃癌前病变大鼠血清中的CEA、CA199、CA7243种肿瘤标志物的水平。3)组合物高剂量(2.38 g/kg)组能够下调TGF-β1 mRNA及其蛋白表达水平,而能够上调Smad4 mRNA及其蛋白表达水平。结论:组合物高剂量(2.38 g/kg)组能够显著改善胃癌前病变大鼠胃黏膜的病理变化,降低血清肿瘤标志物水平,调节TGF-β1和Smad4的蛋白表达,从而纠正TGF-β/Smads信号转导通路的异常变化,有效地治疗胃癌前病变。Objective:To study the efficacy of garlic YZD composition in the treatment of gastric precancerous lesions,and to further clarify the mechanism of garlic YZD composition in the treatment of gastric precancerous lesions.Methods:The rats were randomly divided into 2 groups:a control group(14 rats)and a model group(144 rats).After 22 weeks of modeling,the rats were randomly divided into 6 groups:a model group,a garlic oil control group,a Weifuchun control group,a garlic YZD composition high,a medium and low dose groups,with 24 rats in each group.They were killed after 13 weeks of continuous administration.After taking the material,the pathological changes of gastric mucosa were observed under light microscope.At the same time,the levels of three tumor markers CEA,CA199 and CA724 in the centrifuged plasma of rats in each group were detected by electrochemiluminescence.Western Blotting and Real-time PCR were used to detect the protein and mRNA expression of TGF-β1 and Smad4 in gastric tissues of rats with gastric precancerous lesions.Results:1)High dose group of garlic YZD composition(2.38 g/kg)could significantly improve the pathological changes of gastric mucosa in rats with gastric precancerous lesions.2)High dose group of garlic YZD composition(2.38g/kg)can significantly reduce the levels of CEA,CA199 and CA724 tumor markers in serum of rats with gastric precancerous lesions.3)High dose group of garlic YZD composition(2.38g/kg)can down regulate the expression level of TGF-βl mRNA and its protein,but up regulate the expression level of Smad4 mRNA and its protein.Conclusion:High dose group of garlic YZD composition(2.38 g/kg)can significantly improve the pathological changes of gastric mucosa in rats with gastric precancerous lesions,reduce the level of serum tumor markers,regulate the protein expression of TGF-β1 and Smad4,so as to correct the abnormal changes of TGF-β1/Smads signal transduction pathway,and effectively treat the precancerous lesions of gastric cancer.

关 键 词：大蒜油 大蒜皂苷 大蒜多糖 组合物 甲基硝基亚硝基胍 大鼠 胃癌前病变 机制探讨 

分 类 号：R273[医药卫生—中西医结合]