胃炎康方对慢性非萎缩性胃炎患者胃泌素相关基因调控通路影响
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摘要
目的采用网络药理学预测胃炎康方的作用靶点,以临床样本验证该靶点的准确性,确定胃炎康方的分子机制。方法采用随机数字表法将112例慢性非萎缩性胃炎患者分为治疗组和对照组各56例。对照组采用西医常规治疗;治疗组予胃炎康方,每日1剂,水煎,每日2次口服。2组均连续治疗4周。分析2组临床疗效。采用生物信息学手段挖掘胃炎康方潜在调控基因,预测其作用于胃炎的靶点。应用免疫组化法分析胃部组织样本以验证胃炎康方的作用机制。结果治疗组总有效率为87.5%(49/56),对照组为78.6%(44/56),2组比较差异无统计学意义(P>0.05)。胃镜显示2组胃部病理学结构均好转,差异无统计学意义(P>0.05)。通过网络药理学对胃炎康方作用的靶基因进行预测,其胃泌素相关的靶基因包括前列腺素G/H合成酶2、B细胞κ轻肽基因增强子抑制因子、磷脂酰肌醇-3激酶催化亚基δ及前列腺素F2α受体。并预测胃炎康方可基由PTGS2→IKBKB的信号通路,抑制胃泌素所致的炎症反应。通过胃炎康方治疗的临床样本分析,基本验证以上推论。结论胃炎康方通过对PTGS2、IKBKB、PIK3CD、PTGFR等靶基因的调控激活相应信号通路而发挥治疗作用。采用网络药理学手段可快速预测复方作用靶点,应用该方法可解释复方对相关疾病的治疗机制,并提供新的研究手段。
Objective To predict the targets of Weiyankang Prescription by means of network pharmacology; To verify the accuracy of the targets with clinical samples to determine the molecular mechanism of Weiyankangprescription. Methods Totally 112 cases of chronic non-atrophic gastritis were divided into treatment group and control group, with 56 cases in each group. The control group was treated with Western medicine, and the treatment group was given Weiyankang Prescription, one dosage a day, decoction, orally twice a day. All were treated continuously for 4 weeks. The bioinformatics method was used to mine the potential regulatory genes of WeiyankangPrescription and predict its target in the treatment of gastritis. The gastric tissue samples were analyzed by immunohistochemistry to verify the mechanism of Weiyankang Prescription. Results The total effective rate was 87.5%(49/56) in the treatment group and 78.6%(44/56) in the control group, without statistical significance(P>0.05). Gastroscopic examination showed that the pathological structure of the stomach in both groups improved, without statistical significance(P>0.05). The target genes of Weiyankang Prescription were predicted by network pharmacology. The gastrin-related target genes included: prostaglandin G/H synthetase 2, B cell kappa light peptide gene enhancer inhibitor, phosphatidylinositol-3 kinase catalyzes the subunit δ and prostaglandin F2α receptor. It was predicted that Weiyankang Prescription could inhibit the inflammatory response caused by gastrin by the signal pathway of PTGS2→IKBKB. Through the analysis of clinical samples of Weiyankang Prescription treatment, the above inferences were basically verified. Conclusion Weiyankang Prescription can activate the corresponding signal pathway by regulating the target genes of PTGS2, IKBKB, PIK3 CD and PTGFR, to realize the treatment of chronic gastritis. The use of network pharmacology can quickly predict the target of the compound acting on the disease. This method provides a new means to explain the therapeutic mechanism of compound prescription for related diseases.
Objective To predict the targets of Weiyankang Prescription by means of network pharmacology; To verify the accuracy of the targets with clinical samples to determine the molecular mechanism of Weiyankangprescription. Methods Totally 112 cases of chronic non-atrophic gastritis were divided into treatment group and control group, with 56 cases in each group. The control group was treated with Western medicine, and the treatment group was given Weiyankang Prescription, one dosage a day, decoction, orally twice a day. All were treated continuously for 4 weeks. The bioinformatics method was used to mine the potential regulatory genes of WeiyankangPrescription and predict its target in the treatment of gastritis. The gastric tissue samples were analyzed by immunohistochemistry to verify the mechanism of Weiyankang Prescription. Results The total effective rate was 87.5%(49/56) in the treatment group and 78.6%(44/56) in the control group, without statistical significance(P>0.05). Gastroscopic examination showed that the pathological structure of the stomach in both groups improved, without statistical significance(P>0.05). The target genes of Weiyankang Prescription were predicted by network pharmacology. The gastrin-related target genes included: prostaglandin G/H synthetase 2, B cell kappa light peptide gene enhancer inhibitor, phosphatidylinositol-3 kinase catalyzes the subunit δ and prostaglandin F2α receptor. It was predicted that Weiyankang Prescription could inhibit the inflammatory response caused by gastrin by the signal pathway of PTGS2→IKBKB. Through the analysis of clinical samples of Weiyankang Prescription treatment, the above inferences were basically verified. Conclusion Weiyankang Prescription can activate the corresponding signal pathway by regulating the target genes of PTGS2, IKBKB, PIK3 CD and PTGFR, to realize the treatment of chronic gastritis. The use of network pharmacology can quickly predict the target of the compound acting on the disease. This method provides a new means to explain the therapeutic mechanism of compound prescription for related diseases.
引文
[1]奚锦要,朱永钦,朱永苹,等.中药复方辨证论治慢性萎缩性胃炎的临床研究进展[J].时珍国医国药,2016,27(12):2978-2980.
[2]郭昱,郭霞,姚希贤.慢性萎缩性胃炎胃泌素、生长抑素、表皮生长因子、血管活性肠肽的测定及临床意义[J].世界华人消化杂志,2003,11(5):531-534.
[3]何甜,唐慧,郭强,等.趋化因子10在慢性非萎缩性胃炎、胃癌癌前病变及胃癌中的表达及意义[J].重庆医学,2014,43(4):388-390.
[4]黄懋敏,董丹丹,亓丹丹,等.慢性萎缩性胃炎患者Hp感染与TGF-βRⅡ、IL-6和TNF-α的表达研究[J].中国免疫学杂志,2018,34(5):751-756.
[5]林志强,王大璇,洪珊珊,等.香砂六君子汤对菌致慢性萎缩性胃炎TLR信号通路的影响[J].中国中药杂志,2016,41(16):3078-3083.
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[7]中华医学会消化内镜学分会.慢性胃炎的内镜分型分级标准及治疗的试行意见[J].中华消化内镜杂志,2004,21(2):77-78.
[8]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002.
[9] CUI M, YU W, DONG J, et al. Downregulation of ABI1 expression affectstheprogressionandprognosisofhumangastric carcinoma[J]. Med Oncol,2010,27(3):632-639.
[10]崔梅花,张欣焱,乙国兴,等.酿酒酵母菌抗原在炎症性肠病结肠组织中的表达及意义[J].中华临床医师杂志(电子版),2011,5(4):986-989.
[11]乔世峰,王季堃,李世正,等.PIK3CD基因沉默可抑制胃癌HGC-27细胞的体外增殖和迁移[J].肿瘤,2015,35(1):24-30.
[12]陈国胜.胃泌素/CCK2R通过JAK2/STAT3通路上调COX-2表达诱导胃癌细胞增殖[D].南京:南京医科大学,2015.
[13]张利红,程静静,夏和先,等.幽门螺杆菌感染与慢性胃炎和胃癌的致病机制研究进展[J].国际检验医学杂志,2016,37(22):3165-3167.
[14] CAO X, TSUKAMOTO T, NOZAKI K, et al. Severity of gastritis determinesglandularstomachcarcinogenesisinhelicobacter pylori-infected mongolian gerbils[J]. Cancer Sci,2007,98(4):478-483.
[15]喻德林,胡希亚.幽门螺杆菌根除性治疗对慢性胃炎患者胃泌素及细胞因子的影响[J].现代消化及介入诊疗,2016,21(4):619-622.
[16] SAUKKONEN K, RINTAHAKA J, SIVULA A, et al. Cyclooxygenase-2and gastric carcinogenesis[J]. APMIS,2003,111(10):915-925.
[17] WANG Q S, XIANG Y, CUI Y L, et al. Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting LPS-induced iNOS and COX-2 expression via the NF-κB inactivation[J]. PLoS One,2012,7(3):e34122.
[18]陈文标,杨维群,刘立飞,等.胃癌组织中Keap1、IKKβ蛋白表达及意义[J].胃肠病学和肝病学杂志,2016,25(6):638-641.
[19] VELLA V, NICOLOSI M L, GIULIANO S, et al. PPAR-γagonists as antineoplastic agents in cancers with dysregulated IGF axis[J].Front Endocrinol(Lausanne),2017,8:31.
[20]王雷,蔡冰.PIK3CD表达量检测对胃癌临床病理分期及恶性程度的评估价值[J].海南医学院学报,2016,22(9):924-927.
[21]乔世峰,李世正,佟鑫.PIK3CD表达上调与胃癌临床病理特征及患者预后的相关性[J].中国肿瘤生物治疗杂志,2015,22(1):62-66.
[22] BRüCHER B L, LI Y, SCHNABEL P, et al. Genomics, microRNA,epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers[J]. Clin Transl Med,2016,5(1):13.
[23]OLMANMA.BeyondTGF-beta:aprostaglandinpromotes fibrosis[J]. Nat Med,2009,15(12):1360-1361.
[24]李常恩,姚英民,韩少山,等.胆管良性瘢痕组织中前列腺素F2α受体及前列腺素合酶2的表达及意义[J].中国普外基础与临床杂志,2011,18(12):1283-1287.
[2]郭昱,郭霞,姚希贤.慢性萎缩性胃炎胃泌素、生长抑素、表皮生长因子、血管活性肠肽的测定及临床意义[J].世界华人消化杂志,2003,11(5):531-534.
[3]何甜,唐慧,郭强,等.趋化因子10在慢性非萎缩性胃炎、胃癌癌前病变及胃癌中的表达及意义[J].重庆医学,2014,43(4):388-390.
[4]黄懋敏,董丹丹,亓丹丹,等.慢性萎缩性胃炎患者Hp感染与TGF-βRⅡ、IL-6和TNF-α的表达研究[J].中国免疫学杂志,2018,34(5):751-756.
[5]林志强,王大璇,洪珊珊,等.香砂六君子汤对菌致慢性萎缩性胃炎TLR信号通路的影响[J].中国中药杂志,2016,41(16):3078-3083.
[6]中华医学会消化病学分会.中国慢性胃炎共识意见(2017年,上海)[J].中华消化杂志,2017,37(11):721-738.
[7]中华医学会消化内镜学分会.慢性胃炎的内镜分型分级标准及治疗的试行意见[J].中华消化内镜杂志,2004,21(2):77-78.
[8]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002.
[9] CUI M, YU W, DONG J, et al. Downregulation of ABI1 expression affectstheprogressionandprognosisofhumangastric carcinoma[J]. Med Oncol,2010,27(3):632-639.
[10]崔梅花,张欣焱,乙国兴,等.酿酒酵母菌抗原在炎症性肠病结肠组织中的表达及意义[J].中华临床医师杂志(电子版),2011,5(4):986-989.
[11]乔世峰,王季堃,李世正,等.PIK3CD基因沉默可抑制胃癌HGC-27细胞的体外增殖和迁移[J].肿瘤,2015,35(1):24-30.
[12]陈国胜.胃泌素/CCK2R通过JAK2/STAT3通路上调COX-2表达诱导胃癌细胞增殖[D].南京:南京医科大学,2015.
[13]张利红,程静静,夏和先,等.幽门螺杆菌感染与慢性胃炎和胃癌的致病机制研究进展[J].国际检验医学杂志,2016,37(22):3165-3167.
[14] CAO X, TSUKAMOTO T, NOZAKI K, et al. Severity of gastritis determinesglandularstomachcarcinogenesisinhelicobacter pylori-infected mongolian gerbils[J]. Cancer Sci,2007,98(4):478-483.
[15]喻德林,胡希亚.幽门螺杆菌根除性治疗对慢性胃炎患者胃泌素及细胞因子的影响[J].现代消化及介入诊疗,2016,21(4):619-622.
[16] SAUKKONEN K, RINTAHAKA J, SIVULA A, et al. Cyclooxygenase-2and gastric carcinogenesis[J]. APMIS,2003,111(10):915-925.
[17] WANG Q S, XIANG Y, CUI Y L, et al. Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting LPS-induced iNOS and COX-2 expression via the NF-κB inactivation[J]. PLoS One,2012,7(3):e34122.
[18]陈文标,杨维群,刘立飞,等.胃癌组织中Keap1、IKKβ蛋白表达及意义[J].胃肠病学和肝病学杂志,2016,25(6):638-641.
[19] VELLA V, NICOLOSI M L, GIULIANO S, et al. PPAR-γagonists as antineoplastic agents in cancers with dysregulated IGF axis[J].Front Endocrinol(Lausanne),2017,8:31.
[20]王雷,蔡冰.PIK3CD表达量检测对胃癌临床病理分期及恶性程度的评估价值[J].海南医学院学报,2016,22(9):924-927.
[21]乔世峰,李世正,佟鑫.PIK3CD表达上调与胃癌临床病理特征及患者预后的相关性[J].中国肿瘤生物治疗杂志,2015,22(1):62-66.
[22] BRüCHER B L, LI Y, SCHNABEL P, et al. Genomics, microRNA,epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers[J]. Clin Transl Med,2016,5(1):13.
[23]OLMANMA.BeyondTGF-beta:aprostaglandinpromotes fibrosis[J]. Nat Med,2009,15(12):1360-1361.
[24]李常恩,姚英民,韩少山,等.胆管良性瘢痕组织中前列腺素F2α受体及前列腺素合酶2的表达及意义[J].中国普外基础与临床杂志,2011,18(12):1283-1287.