丹芪祛瘀止痛颗粒对慢性萎缩性胃炎癌前病变大鼠PTEN、RUNX3基因甲基化的影响
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摘要
目的:探讨丹芪祛瘀止痛颗粒对PLGC大鼠胃黏膜组织PTEN、RUNX3基因甲基化及PTEN、RUNX3基因mRNA表达的影响。方法:将80只大鼠按体质量随机分为空白组、模型组、维酶素组、丹芪祛瘀止痛颗粒组。除空白组外,其余各组均创建实验性大鼠PLGC模型。造模后,维酶素组和丹芪祛瘀止痛颗粒组给予相应药物灌胃,空白组和模型组以0.9%Nacl溶液灌胃,1次/d。灌胃12周后,观察各组胃组织病理学改变,MSP法检测PETN、Runx3基因甲基化及RT-PCR法检测PETN、Runx3 mRNA表达。结果:维酶素组、丹芪祛瘀止痛颗粒组均能改善胃黏膜组织炎症、萎缩、肠上皮化生、异型增生,其中以丹芪祛瘀止痛颗粒组最佳;造模后,模型组PTEN、RUNX3基因甲基化比率明显高于空白组(P<0.01),药物干预后,维酶素组甲基化比率下调,与模型组比较,差异具有统计学意义(P<0.05);丹芪祛瘀止痛颗粒组与模型组比较,差异具有显著统计学意义(P<0.01),且丹芪祛瘀止痛颗粒组PTEN、RUNX3基因甲基化比率明显低于维酶素组(P<0.01)。RT-PCR结果显示,模型组大鼠PTEN mRNA、RUNX3 mRNA较模型组显著下降(P<0.01),药物干预后PTEN mRNA、RUNX3 mRNA显著上调,其中以丹芪祛瘀止痛颗粒组效果最佳,差异具有统计学意义(维酶素组P<0.05,丹芪祛瘀止痛颗粒组P<0.01)。结论:丹芪祛瘀止痛颗粒可明显改善PLGC大鼠胃黏膜组织萎缩、肠上皮化生及异型增生情况,其作用机制可能是通过降低基因甲基化比率,上调PTEN、RUNX3基因mRNA表达实现的。
Objective: To observe the effect of Danqi Quyu Zhitong Granule on the PTEN and RUNX3 gene methylation and expressions of PTEN and RUNX3 mRNA on gastric mucosa in rats with PLGC.Methods: Eighty rats were divided into blank group,model group,vitacoenzyme group and Danqi Quyu Zhitong granule group randomly.Except the blank group,the other groups were created PLGC rat model.After modeling,the vitacoenzyme group and Danqi Quyu Zhitong granule group were fed with corresponding drugs.The blank group and model group were treated with 0.9% Na Cl solution orally,once a day.After 12 weeks of intragastric administration,the pathological changes of gastric tissue were observed.The expressions of PETN and Runx3 gene methylation were detected by MSP method and the expressions of PTEN and Runx3 mRNA were detected by RT-PCR method.Results: The vitacoenzyme group and Danqi Quyu Zhitong Granule group can improve gastric mucosa inflammation,atrophy,intestinal metaplasia and dysplasia,and the Danqi Quyu Zhitong Granule group was the best.After modeling,the PTEN and RUNX3 gene methylation in the model group were significantly higher than those of the blank group(P < 0.01).After drug intervention,the methylation rate of the vitacoenzyme group was decreased and the difference was statistically significant compared with that of the model group(P < 0.05).And the difference was also statistically significant compared with that of Danqi Quyu Zhitong Granule group(P < 0.01),while PTEN and RUNX3 gene methylation of Danqi Quyu Zhitong Granule group were significantly lower than those of the vitacoenzyme group(P < 0.01).The results of RT-PCR showed that the PTEN mRNA and RUNX3 mRNA in the model group decreased significantly compared with those of the blank group(P < 0.01).PTEN and RUNX3 mRNA were significantly up-regulated after drug intervention.The Danqi Quyu Zhitong Granule group had the best effect and the difference was statistically significant(vitacoenzyme group P < 0.05,Danqi Quyu Zhitong Granule group P < 0.01).Conclusion: Danqi Quyu Zhitong Granule can significantly improve the atrophy,intestinal metaplasia and dysplasia of gastric mucosal tissue.Its mechanism may through the reduction of gene methylation ratio and up-regulation of the expression of PTEN RUNX3 mRNA implementation.
Objective: To observe the effect of Danqi Quyu Zhitong Granule on the PTEN and RUNX3 gene methylation and expressions of PTEN and RUNX3 mRNA on gastric mucosa in rats with PLGC.Methods: Eighty rats were divided into blank group,model group,vitacoenzyme group and Danqi Quyu Zhitong granule group randomly.Except the blank group,the other groups were created PLGC rat model.After modeling,the vitacoenzyme group and Danqi Quyu Zhitong granule group were fed with corresponding drugs.The blank group and model group were treated with 0.9% Na Cl solution orally,once a day.After 12 weeks of intragastric administration,the pathological changes of gastric tissue were observed.The expressions of PETN and Runx3 gene methylation were detected by MSP method and the expressions of PTEN and Runx3 mRNA were detected by RT-PCR method.Results: The vitacoenzyme group and Danqi Quyu Zhitong Granule group can improve gastric mucosa inflammation,atrophy,intestinal metaplasia and dysplasia,and the Danqi Quyu Zhitong Granule group was the best.After modeling,the PTEN and RUNX3 gene methylation in the model group were significantly higher than those of the blank group(P < 0.01).After drug intervention,the methylation rate of the vitacoenzyme group was decreased and the difference was statistically significant compared with that of the model group(P < 0.05).And the difference was also statistically significant compared with that of Danqi Quyu Zhitong Granule group(P < 0.01),while PTEN and RUNX3 gene methylation of Danqi Quyu Zhitong Granule group were significantly lower than those of the vitacoenzyme group(P < 0.01).The results of RT-PCR showed that the PTEN mRNA and RUNX3 mRNA in the model group decreased significantly compared with those of the blank group(P < 0.01).PTEN and RUNX3 mRNA were significantly up-regulated after drug intervention.The Danqi Quyu Zhitong Granule group had the best effect and the difference was statistically significant(vitacoenzyme group P < 0.05,Danqi Quyu Zhitong Granule group P < 0.01).Conclusion: Danqi Quyu Zhitong Granule can significantly improve the atrophy,intestinal metaplasia and dysplasia of gastric mucosal tissue.Its mechanism may through the reduction of gene methylation ratio and up-regulation of the expression of PTEN RUNX3 mRNA implementation.
引文
[1]陈万青,郑荣寿,张思维,等.2012年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2016,25(1):1-8.
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[13]王志红,鲍德明,石振旺,等.溃疡型胃癌和癌前病变中PTEN、Survivin的表达及临床意义[J].临床与实验病理学杂志,2015,10:1153-1156.
[14]宁玉凤,杨翠兰,李福善.慢萎散治疗胃阴不足证慢性萎缩性胃炎的临床分析[J].中国实验方剂学杂志,2016,22(13):173-176.
[15]李希新,苏明廉.当代中药临床应用[M].济南:济南出版社,1999:675-680.
[16]赵唯含,高康丽,李宁飞,等.黄芪、三七及其配伍对慢性萎缩性胃炎大鼠胃组织Hedgehog信号通路的调节作用[J].中华中医药杂志,2016,31(5):1951-1955.
[17]王宏虹,刘华钢,刘丽敏.β-榄香烯抗肿瘤作用机制研究概况[J].药物评价研究,2009,32(2):140-143.
[18]杨巧芳.牛兴东主任医师运用调气活血解毒法治疗慢性萎缩性胃炎经验[J].辽宁中医药大学学报,2011,13(12):129-131.
[19]张金丽,王彦刚,周盼盼,等.化浊解毒和胃方对慢性萎缩性胃炎癌前病变患者胃液成分的影响[J].中医杂志,2014,55(5):400-403.
[20]张汝卫.益胃汤治疗慢性萎缩性胃炎30例[J].中国中医药现代远程教育,2013,13(7):7-8.
[21]李锦绣.丁香现代药理研究进展[J].实用中医药杂志,2002,18(6):54.
[2]Torre L A,Bray F,Siegel R L,et al.Global cancer statistics,2012[J].Ca A Cancer Journal for Clinicians,2015,65(2):87-108.
[3]李志钢,张伟,邱作成,等.解毒化瘀健脾方及拆方对胃黏膜异型增生大鼠多基因去甲基化诱导表达的比较[J].世界华人消化杂志,2014,22(13):1820-1825.
[4]刘玺,陈卫刚,李睿,等.新疆哈萨克族胃癌中Smad4基因启动子的甲基化状态[J].世界华人消化杂志,2013,21(20):1907-1913.
[5]刘长发,杨春壮,董嘉楠.丹芪祛瘀止痛颗粒治疗慢性萎缩性胃炎临床疗效观察[J].牡丹江医学院学报,2013,34(1):68-69.
[6]张雅丽,刘长发.丹芪祛瘀止痛颗粒治疗幽门螺杆菌相关性萎缩性胃炎43例[J].中国中医药科技,2014,21(5):575-576.
[7]张雅丽,刘长发,宋伟亮.丹芪祛瘀止痛颗粒治疗萎缩性胃炎40例疗效分析[J].中国中医药科技,2013,20(6):667.
[8]王少明,林才经,杨春波,等.大鼠胃黏膜癌前病变实验动物模型的建立[J].药学实践杂志,2005,23(5):271-272.
[9]Kulis M,Esteller M.DNA methylation and cancer.Adv Genet[J].Advances in Genetics,2010,70(10):27-56.
[10]Huang B,Qu Z,Ong C W,et al.RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptorα[J].Oncogene,2012,31(4):527-534.
[11]Takashima S,Hartenstein V.Genetic control of intestinal stem cell specification and development:a comparative view[J].Stem Cell Reviews,2012,8(2):597-608.
[12]武雪亮,王立坤,薛军,等.RUNX3与消化系肿瘤的研究进展[J].基础医学与临床,2014,34(6):866-869.
[13]王志红,鲍德明,石振旺,等.溃疡型胃癌和癌前病变中PTEN、Survivin的表达及临床意义[J].临床与实验病理学杂志,2015,10:1153-1156.
[14]宁玉凤,杨翠兰,李福善.慢萎散治疗胃阴不足证慢性萎缩性胃炎的临床分析[J].中国实验方剂学杂志,2016,22(13):173-176.
[15]李希新,苏明廉.当代中药临床应用[M].济南:济南出版社,1999:675-680.
[16]赵唯含,高康丽,李宁飞,等.黄芪、三七及其配伍对慢性萎缩性胃炎大鼠胃组织Hedgehog信号通路的调节作用[J].中华中医药杂志,2016,31(5):1951-1955.
[17]王宏虹,刘华钢,刘丽敏.β-榄香烯抗肿瘤作用机制研究概况[J].药物评价研究,2009,32(2):140-143.
[18]杨巧芳.牛兴东主任医师运用调气活血解毒法治疗慢性萎缩性胃炎经验[J].辽宁中医药大学学报,2011,13(12):129-131.
[19]张金丽,王彦刚,周盼盼,等.化浊解毒和胃方对慢性萎缩性胃炎癌前病变患者胃液成分的影响[J].中医杂志,2014,55(5):400-403.
[20]张汝卫.益胃汤治疗慢性萎缩性胃炎30例[J].中国中医药现代远程教育,2013,13(7):7-8.
[21]李锦绣.丁香现代药理研究进展[J].实用中医药杂志,2002,18(6):54.