基于TGF-β1/Smad3通路探讨脾胃培源方对慢性萎缩性胃炎大鼠干预作用
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摘要
目的观察脾胃培源方对慢性萎缩性胃炎(chronic atrophic gastritis,CAG)大鼠血清胃蛋白酶原I(pepsinogenI, PGⅠ)、胃蛋白酶原Ⅱ(pepsinogenⅡ, PGⅡ)、胃泌素(gastrin-17, G-17)水平的影响,通过研究转化生长因子β1(transforming growth factor-β1, TGF-β1)和Smad3蛋白在CAG大鼠胃组织中的表达,探讨TGF-β1/Smad3信号传导通路在CAG发病过程中的作用以及脾胃培源方的治疗机制。方法选用SPF级Wistar雄性大鼠100只,随机分为:空白对照组、模型组、维酶素组、脾胃培源方(高、中、低剂量)组,采用幽门弹簧植入术配合高盐热淀粉糊灌胃法制备CAG大鼠模型。造模成功后,各组予以相关干预,连续灌胃4周,4周后处死大鼠取血清及胃组织。通过HE染色观察大鼠胃组织病理学的改变,并采用Elisa法和Western blot法检测血清PGⅠ、PGⅡ、G-17水平及TGF-β1、Smad3蛋白表达。结果与空白对照组比较,模型组血清PGⅠ、G-17水平及Smad3蛋白表达显著降低(P<0.05),TGF-β1蛋白表达明显上升(P<0.05);与模型组比较,脾胃培源方组和维酶素组血清PGⅠ、G-17水平及Smad3蛋白表达明显上升(P<0.05),TGF-β1蛋白表达明显降低(P<0.05),血清PGⅡ均未见明显变化,差异无统计学意义(P>0.05);维酶素组和脾胃培源方(高、中、低剂量组)4组间采取两两比较,差异无统计学意义(P>0.05)。结论脾胃培源方能明显改善CAG大鼠的胃组织损伤,下调胃组织TGF-β1蛋白表达及上调Smad3蛋白的表达,说明TGF-β1/Smad3信号转导通路参与了CAG发病过程,脾胃培源方治疗CAG可能通过干预该通路的表达而实现。
Objective To investigate the effect of Piwei Peiyuan Decoction on the serum levels of pepsinogen I(PG I),pepsinogen II(PG II), and gastrin-17(G-17) in rats with chronic atrophic gastritis(CAG), as well as the role of the TGF-β1/Smad3 signaling pathway in the development of CAG and the therapeutic mechanism of Piwei Peiyuan Decoction based on the expression of transforming growth factor-β1(TGF-β1) and Smad3 in gastric tissue. Methods A total of 100 specific pathogenfree male Wistar rats were randomly divided into blank control group, model group, vitacoenzyme group, and high-, middle-, and low-dose Piwei Peiyuan Decoction groups. A rat model of CAG was established by spring implantation at the pylorus and high-salt hot starch paste by gavage. After the model was successfully established, each group was given the corresponding treatment, and after 4 consecutive weeks of gavage, the rats were sacrificed to collect serum and gastric tissue.HE staining was performed to observe the pathological changes of gastric tissue, and ELISA and Western blot were used to measure the serum levels of PG I, PG II, and G-17 and the protein expression of TGF-β1 and Smad3. Results Compared with the blank control group, the model group had significant reductions in the serum levels of PG I and G-17 and the protein expression of Smad3(P<0.05) and a significant increase in the protein expression of TGF-β1(P<0.05). Compared with the model group, the Piwei Peiyuan Decoction groups and the vitacoenzyme group had significant increases in the serum levels of PG I and G-17 and the protein expression of Smad3(P <0.05) and a significant reduction in the protein expression of TGF-β1(P <0.05). There was no significant change or difference in the serum level of PG II(P >0.05). There were no significant differences in the above indices between any two of the vitacoenzyme group and the high-, middle-, and low-dose Piwei Peiyuan Decoction groups(P >0.05). Conclusion Piwei Peiyuan Decoction can significantly improve gastric injury, downregulate the protein expression of TGF-β1, and upregulate the protein expression of Smad3 in CAG rats,suggesting that the TGF-β1/Smad3 signaling pathway may be involved in the development of CAG. Piwei Peiyuan Decoction may be therapeutic against CAG by exerting an intervention effect on this signaling pathway.
Objective To investigate the effect of Piwei Peiyuan Decoction on the serum levels of pepsinogen I(PG I),pepsinogen II(PG II), and gastrin-17(G-17) in rats with chronic atrophic gastritis(CAG), as well as the role of the TGF-β1/Smad3 signaling pathway in the development of CAG and the therapeutic mechanism of Piwei Peiyuan Decoction based on the expression of transforming growth factor-β1(TGF-β1) and Smad3 in gastric tissue. Methods A total of 100 specific pathogenfree male Wistar rats were randomly divided into blank control group, model group, vitacoenzyme group, and high-, middle-, and low-dose Piwei Peiyuan Decoction groups. A rat model of CAG was established by spring implantation at the pylorus and high-salt hot starch paste by gavage. After the model was successfully established, each group was given the corresponding treatment, and after 4 consecutive weeks of gavage, the rats were sacrificed to collect serum and gastric tissue.HE staining was performed to observe the pathological changes of gastric tissue, and ELISA and Western blot were used to measure the serum levels of PG I, PG II, and G-17 and the protein expression of TGF-β1 and Smad3. Results Compared with the blank control group, the model group had significant reductions in the serum levels of PG I and G-17 and the protein expression of Smad3(P<0.05) and a significant increase in the protein expression of TGF-β1(P<0.05). Compared with the model group, the Piwei Peiyuan Decoction groups and the vitacoenzyme group had significant increases in the serum levels of PG I and G-17 and the protein expression of Smad3(P <0.05) and a significant reduction in the protein expression of TGF-β1(P <0.05). There was no significant change or difference in the serum level of PG II(P >0.05). There were no significant differences in the above indices between any two of the vitacoenzyme group and the high-, middle-, and low-dose Piwei Peiyuan Decoction groups(P >0.05). Conclusion Piwei Peiyuan Decoction can significantly improve gastric injury, downregulate the protein expression of TGF-β1, and upregulate the protein expression of Smad3 in CAG rats,suggesting that the TGF-β1/Smad3 signaling pathway may be involved in the development of CAG. Piwei Peiyuan Decoction may be therapeutic against CAG by exerting an intervention effect on this signaling pathway.
引文
[1]李军祥,陈誩,吕宾,等.慢性萎缩性胃炎中西医结合诊疗共识意见(2017年)[J].中国中西医结合消化杂志,2018,26(2):121-131.
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[5]史瑞,李晓红,方蕾,等.弹簧幽门植入术结合高盐热淀粉糊灌胃诱导大鼠萎缩性胃炎模型的方法及评价[J].世界华人消化杂志,2011,19(10):1001-1008.
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[10]陈仁龙.健脾活血法治疗慢性萎缩性胃炎的疗效观察及对转化生长因子(TGF-β1)、Smad3表达的影响[D].南京:南京中医药大学,2017:11-13.
[11]蔡蔚,谢海平,龙蠡,等.马归液对腺性膀胱炎模型大鼠TGF-β1、EGF-β的影响[J].湖南中医药大学学报,2018,38(8):870-874.
[12]刘镕,赵琴平,董惠芬,等.TGF-β信号传导通路及其生物学功能[J].中国病原生物学杂志,2014,9(1):77-83.
[13]谢晶日,孙健伟,梁国英.益气养阴活血法对慢性萎缩性胃炎胃黏膜细胞凋亡和基因调控的影响[J].时珍国医国药,2011,22(9):295-296.
[14]刘海燕,陈军贤.香砂养胃丸对慢性萎缩性胃炎患者胃黏膜TGF-β1、Smad3表达的影响[J].中药材,2014,37(3):540-542.
[15]戴卫波,梅全喜,曾聪彦,等.布渣叶不同提取部位对大鼠胃液分泌功能的影响研究[J].时珍国医国药,2015,21(3):34-36.
[2]张声生,李乾构,唐旭东,等.慢性萎缩性胃炎中医诊疗共识意见[J].中医杂志,2010,51(8):749-753.
[3]李仲启,傅汉中.胃肠道癌前病变和癌前疾病研究现状[J].临床消化病杂志,2015,27(3):183-185.
[4]杨宗保,葛来安,何晓晖,等.双蒲散对慢性萎缩性胃炎大鼠胃黏膜细胞TGF-β1/Smad3信号通路的影响[J].江西中医药,2016,47(1):34-37.
[5]史瑞,李晓红,方蕾,等.弹簧幽门植入术结合高盐热淀粉糊灌胃诱导大鼠萎缩性胃炎模型的方法及评价[J].世界华人消化杂志,2011,19(10):1001-1008.
[6]陈佳,李守英,徐红,等.慢性萎缩性胃炎的研究进展[J].中国老年学杂志,2013,33(14):3540-3542.
[7]朱春平,赵建业,申晓军,等.血清胃泌素-17联合胃蛋白酶原检测对胃癌诊断价值的多中心临床研究[J].中华消化内镜杂志,2017,34(1):19-23.
[8]孙雪飞,何旭.血清胃蛋白酶原与胃泌素检测对慢性萎缩性胃炎的诊断价值[J].湖南师范大学学报(医学版),2016,13(5):115-117.
[9]姚文君,郑学东,苗得露.血清胃蛋白酶原、胃泌素-17与胃癌及慢性萎缩性胃炎的相关性研究[J].临床合理用药杂志,2017,10(8):108-109.
[10]陈仁龙.健脾活血法治疗慢性萎缩性胃炎的疗效观察及对转化生长因子(TGF-β1)、Smad3表达的影响[D].南京:南京中医药大学,2017:11-13.
[11]蔡蔚,谢海平,龙蠡,等.马归液对腺性膀胱炎模型大鼠TGF-β1、EGF-β的影响[J].湖南中医药大学学报,2018,38(8):870-874.
[12]刘镕,赵琴平,董惠芬,等.TGF-β信号传导通路及其生物学功能[J].中国病原生物学杂志,2014,9(1):77-83.
[13]谢晶日,孙健伟,梁国英.益气养阴活血法对慢性萎缩性胃炎胃黏膜细胞凋亡和基因调控的影响[J].时珍国医国药,2011,22(9):295-296.
[14]刘海燕,陈军贤.香砂养胃丸对慢性萎缩性胃炎患者胃黏膜TGF-β1、Smad3表达的影响[J].中药材,2014,37(3):540-542.
[15]戴卫波,梅全喜,曾聪彦,等.布渣叶不同提取部位对大鼠胃液分泌功能的影响研究[J].时珍国医国药,2015,21(3):34-36.