健脾理气方抑制肥大细胞改善十二指肠紧密连接蛋白表达治疗功能性消化不良的机制研究
Mechanism of Jianpi Liqi Decoction in treatment of functional dyspepsia by inhibiting mast cell activation and improving the expression of tight junction proteins
- 上海中医药杂志 2021年55卷第11期 页码：91-96
- 作者机构：
1.北京中医医院顺义医院脾胃科（北京 101300）
- 作者简介：
常雄飞，男，博士，医师，主要从事中医药治疗功能性胃肠病临床研究工作
谭海成，副主任医师；E-mail：thch4250@sina.com
- 基金信息：国家自然科学基金项目(82004270);北京市属医院科研培育计划项目(PZ2020024);北京中医医院顺义医院院级课题(SYYJ-201803)
DOI：10.16305/j.1007-1334.2021.2105034
中图分类号：
扫 描 看 全 文
常雄飞, 沈凌宇, 张立宏, 等. 健脾理气方抑制肥大细胞改善十二指肠紧密连接蛋白表达治疗功能性消化不良的机制研究[J]. 上海中医药杂志, 2021,55(11):91-96.
Xiongfei CHANG, Lingyu SHEN, Lihong ZHANG, et al. Mechanism of Jianpi Liqi Decoction in treatment of functional dyspepsia by inhibiting mast cell activation and improving the expression of tight junction proteins[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(11):91-96.
常雄飞, 沈凌宇, 张立宏, 等. 健脾理气方抑制肥大细胞改善十二指肠紧密连接蛋白表达治疗功能性消化不良的机制研究[J]. 上海中医药杂志, 2021,55(11):91-96. DOI： 10.16305/j.1007-1334.2021.2105034.
Xiongfei CHANG, Lingyu SHEN, Lihong ZHANG, et al. Mechanism of Jianpi Liqi Decoction in treatment of functional dyspepsia by inhibiting mast cell activation and improving the expression of tight junction proteins[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(11):91-96. DOI： 10.16305/j.1007-1334.2021.2105034.
摘要
目的,2,探索健脾理气方通过抑制十二指肠肥大细胞（MC）脱颗粒、改善十二指肠紧密连接蛋白（TJs）表达、恢复肠道屏障功能，治疗功能性消化不良（FD）的机制。,方法,2,6周龄SPF级SD雄性大鼠24只，随机分为对照组、模型组、中药组及拮抗剂组，每组6只。除对照组外，其余各组大鼠采用夹尾应激方法建立FD模型。造模结束后，对照组及模型组予纯净水灌胃，中药组予健脾理气方水煎剂灌胃，拮抗剂组予促肾上腺皮质激素释放激素（CRH）拮抗剂腹腔注射。干预结束后取十二指肠，采用Western blot法测定局部CRH主要受体1（CRHR1）、MC标记性蛋白类胰蛋白酶（Tryptase）及蛋白酶激活受体2（PAR-2）、肌球蛋白轻链激酶（MLCK）及TJs（JAM-A、ZO-1、claudin-1）表达情况。,结果,2,与对照组比较，模型组大鼠十二指肠CRHR1、Tryptase、PAR-2、MLCK表达量显著升高（,P,<,0.05），而TJs（JAM-A、ZO-1、claudin-1）表达下调（,P,<,0.05）。与模型组比较，中药组及拮抗剂组大鼠CRHR1、Tryptase、PAR-2、MLCK表达下调（,P,<,0.05），同时TJs（JAM-A、ZO-1、claudin-1）表达量显著升高（,P,<,0.05）。,结论,2,CRH介导的MC激活，释放炎症介质，下调十二指肠局部TJs表达，导致屏障受损可能是FD发病机制之一，而健脾理气方可能通过抑制该损伤性通路，恢复十二指肠局部屏障功能，对FD起到治疗作用。
Abstract
Objective,2,To explore the mechanism of Jianpi Liqi Decoction in the treatment of functional dyspepsia (FD) by inhibiting degranulation of duodenal mast cells (MC), improving the expression of duodenal tight junction proteins (TJs) and restoring intestinal barrier function., Methods,2,Twenty-four 6-week-old SPF male SD rats were randomly divided into control group, model group, traditional Chinese medicine treatment group and CRH antagonist group, 6 rats in each grpup. Except for the control group, the FD model was established by tail clamping stress in other groups. After the establishment of the model, the control group and the model group were given pure water gavage, the traditional Chinese medicine treatment group given Jianpi Liqi Decoction gavage and the CRH antagonist group injected with antagonist intraperitoneally. After the intervention, the duodenum was taken and the expressions of corticotropin releasing hormone (CRH) major receptor 1 (CRHR1), MC marker protein trypsin (Tryptase), protease activated receptor 2 (PAR-2), myosin light chain kinase (MLCK), and TJs (JAM-A, ZO-1, claudin-1) in the duodenum were determined by Western blot.,Results,2,Compared with the control group, the expressions of CRHR1, Tryptase, PAR-2, MLCK in the duodenum of the model group were significant increased (,P,<,0.05), while the expressions of TJs (JAM-A, ZO-1, claudin-1) were down-regulated (,P,<,0.05). Compared with the model group, the expressions of CRHR1, Tryptase, PAR-2 and MLCK in the traditional Chinese medicine group and CRH antagonist group were down-regulated, while the expression of TJs (JAM-A, ZO-1, claudin-1) was significantly increased.,Conclusion,2,CRH-mediated activation of MC, release of inflammatory mediators and down-regulation of local TJs expression in the duodenum resulting in barrier damage may be one of the pathogenesis of FD, and Jianpi Liqi Decoction may inhibit the injury pathway, restore the function of local duodenal barrier and play a therapeutic role in FD.
关键词
功能性消化不良健脾理气方十二指肠促肾上腺皮质激素释放激素肥大细胞紧密连接蛋白肠道屏障中药研究
Keywords
functional dyspepsiaJianpi Liqi DecoctionduodenumCRHmast cellstight junction proteinsintestinal barriertraditional Chinese herbal medicine research
references
MAHADEVA S, FORD A C. Clinical and epidemiological differences in functional dyspepsia between the East and the West[J]. Neurogastroenterol Motil, 2016, 28(2): 167-174.
MIWA H, OSHIMA T, TOMITA T, et al. Recent understanding of the pathophysiology of functional dyspepsia: role of the duodenum as the pathogenic center[J]. J Gastroenterol, 2019, 54(4): 305-311.
JUNG H K, TALLEY N J. Role of the duodenum in the pathogenesis of functional dyspepsia: a paradigm shift[J]. J Neurogastroenterol Motil, 2018, 24(3): 345-354.
KOMORI K, IHARA E, MINODA Y, et al. The altered mucosal barrier function in the duodenum plays a role in the pathogenesis of functional dyspepsia[J]. Dig Dis Sci, 2019, 64(11): 3228-3239.
VANHEEL H, VICARIO M, VANUYTSEL T, et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia[J]. Gut, 2014, 63(2): 262-271.
TAKI M, OSHIMA T, LI M, et al. Duodenal low-grade inflammation and expression of tight junction proteins in functional dyspepsia[J]. Neurogastroenterol Motil, 2019, 31(10): e13576.
BEECKMANS D, RIETHORST D, AUGUSTIJNS P, et al. Altered duodenal bile salt concentration and receptor expression in functional dyspepsia[J]. United European Gastroenterol J, 2018, 6(9): 1347-1355.
朱春洋，赵静怡，张声生. 四逆散对FD大鼠十二指肠杯状细胞及MUC2的影响[J]. 世界中医药，2020, 15(11): 1575-1584.
TAKASHIMA S, TANAKA F, KAWAGUCHI Y, et al. Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice[J]. Neurogastroenterol Motil, 2020, 32(7): e13841.
张声生，赵鲁卿. 功能性消化不良中医诊疗专家共识意见（2017）[J]. 中华中医药杂志，2017, 32(6): 2595-2598.
ZHANG S S, ZHAO L Q, WANG H B, et al. Efficacy of modified LiuJunZi decoction on functional dyspepsia of spleen-deficiency and qi-stagnation syndrome: a randomized controlled trial[J]. BMC Complement Altern Med, 2013(13): 54.
常雄飞. 健脾理气方通过cAMP和NF-κB通路修复十二指肠紧密连接治疗功能性消化不良的机制[D]. 北京：北京中医药大学，2018.
郭海军，林洁，李国成，等. 功能性消化不良的动物模型研究[J]. 中国中西医结合消化杂志，2001, 9(3): 141-142.
WAUTERS L, TALLEY N J, MALKER M M, et al. Novel concepts in the pathophysiology and treatment of functional dyspepsia[J]. Gut, 2020, 69(3): 591-600.
PARADIS T, BÈGUE H, BASMACIYAN L, et al. Tight junctions as a key for pathogens invasion in intestinal epithelial cells[J]. Int J Mol Sci, 2021, 22(5): 2506.
NASCIMENTO J C, MATHEUS V A, OLIVEIRA R B, et al. High-fat diet induces disruption of the tight junction-mediated paracellular barrier in the proximal small intestine before the onset of type 2 diabetes and endotoxemia[J/OL]. Dig Dis Sci, 2020[2021-05-10]. https://pubmed.ncbi.nlm.nih.gov/33104937/https://pubmed.ncbi.nlm.nih.gov/33104937/.
VAN ITALLIE C M, ANDERSON J M. Architecture of tight junctions and principles of molecular composition[J]. Semin Cell Dev Biol, 2014(36): 157-165.
XU W, LU J, CHEN Y, et al. Impairment of CRH in the intestinal mucosal epithelial barrier of pregnant Bama miniature pig induced by restraint stress[J]. Endocr J, 2021, 68(4): 485-502.
SAGAMI Y, SHIMADA Y, TAYAMA J, et al. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome[J]. Gut, 2004, 53(7): 958-964.
ZHU H L, PI D A, LENG W B, et al. Asparagine preserves intestinal barrier function from LPS-induced injury and regulates CRF/CRFR signaling pathway[J]. Innate Immun, 2017, 23(6): 546-556.
VANUYTSEL T, MANROOY S V, VANHEEL H, et al. Psychological stress and corticotropin releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism[J]. Gut, 2014, 63(8): 1293-1299.
ZHONG C J, WANG K, ZHANG L, et al. Mast cell activation is involved in stress-induced epithelial barrier dysfunction in the esophagus[J]. J Dig Dis, 2015, 16(4): 186-196.
HAGIWARA S I, KAUSHAL E, PARUTHIYIL S, et al. Gastric corticotropin-releasing factor influences mast cell infiltration in a rat model of functional dyspepsia[J]. PLoS One, 2018, 13(9): e0203704.
LABUS J S, HUBBARD C S, BUELLER J, et al. Impaired emotional learning and involvement of the corticotropin-releasing factor signaling system in patients with irritable bowel syndrome[J]. Gastroenterology, 2013, 145(6): 1253-1261.
BUENO L, FIORAMONTI J. Protease-activated receptor 2 and gut permeability: a review[J]. Neurogastroenterol Motil, 2008, 20(6): 580-587.
0
浏览量
474
下载量
0
CSCD
7
CNKI被引量
- 网络PDF下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 沪ICP备13044091号
沪公网安备 31011502015228号 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
- 总访问量：70535 今日访问量：16