化瘀解毒益气法对胃癌前病变模型大鼠p16基因甲基化的影响  

The Regulation of Huayu Jiedu Yiqi Principle on p16 Gene Methylation in Rats with Gastric Precancerous Lesion

作　　者：邱岳 杨晋翔 李志钢 苏琳[3] 潘雪[3] 

机构地区：[1]北京中医药大学第三附属医院,北京100029 [2]新疆维吾尔自治区中医医院,新疆乌鲁木齐830000 [3]北京中医药大学,北京100029

出　　处：《中医学报》2017年第12期2289-2293,共5页Acta Chinese Medicine

基　　金：北京中医药大学青年教师专项计划(2013-QNJSZX-003)

摘　　要：目的:观察化瘀解毒益气法对胃癌前病变大鼠胃黏膜组织病理学及p16基因甲基化状态的影响。方法:采用低浓度MNNG加服雷尼替丁的方法造模,20周造模成功之后将大鼠随机分为模型组、维甲酸组、益气通络解毒散组,各组治疗干预后,观察各组大鼠胃黏膜变化情况并采用甲基化特异性PCR(methylation-specific PCR,MSP)方法检测各治疗组中p16基因甲基化状态。结果:造模20周后,模型组大鼠胃黏膜出现肠化生、不典型增生等病理改变,而益气通络解毒散组胃黏膜病变程度较轻;益气通络解毒散组p16抑癌基因Cp G岛甲基化阳性率为33.33%,与模型组76.92%比较,差异有统计学意义(P<0.05)。24例胃黏膜病理为肠上皮化生或异型增生大鼠中,有16例p16抑癌基因启动子区域Cp G岛高甲基化状态;而32例非胃癌前病变大鼠中,有23例p16抑癌基因启动子区域Cp G岛非甲基化。经两变量相关分析检验,Spearman系数为0.383 67,P=0.003 5<0.01。结论:化瘀解毒益气法对胃癌前病变胃黏膜细胞p16基因有一定的去甲基化作用,可能通过降低p16抑癌基因启动子区域Cp G岛甲基化水平,改善大鼠胃黏膜腺体的破坏,从而发挥其治疗胃癌前病变的作用。Objective： To observe the effect of Huayu Jiedu Yiqi principle on pathologic tissues of gastric mucosa and methylation status of p16 in rats with gastric precancerous lesion. Methods： Low concentration of MNNG with ranitidine were used to set up model of gastric precancerous lesion. After the model was succeeded at the 20 th weekend,rats were randomly divided into model group,tretinoin group and Yiqi Tongluo Jiedu San group. After treatment,observed the rat gastric mucosa pathological changes,and methylation-specific technique was used to examine the methylation status of p16. Results： 20 weeks after the rat model was built,the rats in the model set were diagnosed to have pathological changes including intestinal metaplasea and atypical hyperplasia. In terms of gastric mucosa pathological changes,Yiqi Tongluo Jiedu San group significantly improved. The positive rate of CpG islandmethylation of p16 tumor suppressor gene in Yiqi Tongluo Jiedu San group was 33. 33%,compared with the model group76. 92%,the difference was statistically significant（ P〈0. 05）. 24 cases of gastric mucosa pathological intestinal metaplasia or dysplasia in rats,there were 16 cases of p16 tumor suppressor gene promoter region CpG island hypermethylation; In 32 non gastric precancerous rats,there were 23 cases of p16 tumor suppressor gene promoter region CpG Island non methylation. By two variables correlation analysis,the Spearman coefficient was 0. 383 67,and P = 0. 003 5 0. 01. Conclusion： Huayu Jiedu Yiqi principle can induce demethylation of p16 in gastric mucosa cells in rats with gastric precancerous lesion. The way can decrease methylation level of CpG island of promoter region of suppressor tumor gene p16 and improve the condition of gastric mucosa gland damage in rats so as to treat gastric precancerous lesion effectively.

关 键 词：胃癌前病变 化瘀解毒益气法 P16基因 甲基化 大鼠 

分 类 号：R273.52[医药卫生—中西医结合]