Mechanism of Shaoyaotang in Regulating Water Metabolism and Intestinal Epithelial Permeability in Ulcerative Colitis Through cAMP/PKA/CREB Signaling Pathway

WU Dongsheng; CAO Hui; CAO Xiaoyang; ZHANG Yu; XIE Nianjia; YANG Yuting; LU Yi; LI Yanhong

doi:10.13422/j.cnki.syfjx.20230704

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Mechanism of Shaoyaotang in Regulating Water Metabolism and Intestinal Epithelial Permeability in Ulcerative Colitis Through cAMP/PKA/CREB Signaling Pathway

更新时间：2023-03-30

- Mechanism of Shaoyaotang in Regulating Water Metabolism and Intestinal Epithelial Permeability in Ulcerative Colitis Through cAMP/PKA/CREB Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 9, Pages: 53-60(2023)
- 作者机构：
  
  1.湖南中医药大学第一附属医院，长沙 410007
  2.南京医科大学，南京 211166
  3.湖南中医药大学，长沙 410208
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230704
  CLC： R2-0;R22;R285.5;R289;R33
- Published：05 May 2023，
  
  Published Online：23 February 2023，
  
  Received：06 September 2022，
- 稿件说明：
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吴东升,曹晖,曹晓阳等.芍药汤通过cAMP/PKA/CREB信号通路调控溃疡性结肠炎水液代谢及肠上皮通透性的作用机制[J].中国实验方剂学杂志,2023,29(09):53-60.

WU Dongsheng,CAO Hui,CAO Xiaoyang,et al.Mechanism of Shaoyaotang in Regulating Water Metabolism and Intestinal Epithelial Permeability in Ulcerative Colitis Through cAMP/PKA/CREB Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(09):53-60.
吴东升,曹晖,曹晓阳等.芍药汤通过cAMP/PKA/CREB信号通路调控溃疡性结肠炎水液代谢及肠上皮通透性的作用机制[J].中国实验方剂学杂志,2023,29(09):53-60. DOI： 10.13422/j.cnki.syfjx.20230704.

WU Dongsheng,CAO Hui,CAO Xiaoyang,et al.Mechanism of Shaoyaotang in Regulating Water Metabolism and Intestinal Epithelial Permeability in Ulcerative Colitis Through cAMP/PKA/CREB Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(09):53-60. DOI： 10.13422/j.cnki.syfjx.20230704.

摘要

目的

基于“大肠主津”理论探讨环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应成分结合蛋白（cAMP/PKA/CREB）信号通路在溃疡性结肠炎（UC）水液代谢及肠上皮通透性中的作用及芍药汤的干预机制。

方法

将60只雄性SD大鼠分为空白组、模型组、美沙拉嗪组（0.42 g·kg

-1

）、芍药汤低、中、高剂量组（11.1、22.2、44.4 g·kg

-1

），每组10只。采用复合病因造模法建立UC湿热内蕴证大鼠模型，空白组和模型组分别给予生理盐水灌胃，美沙拉嗪组给予美沙拉嗪灌胃，芍药汤低、中、高剂量给予对应剂量的芍药汤灌胃，灌胃周期为14 d。观察各组大鼠腹泻评分及粪便含水率变化，采用酶联免疫吸附测定法（ELISA）检测血浆二胺氧化酶（DAO）、

-乳酸含量，免疫组化法检测各组大鼠结肠组织中水通道蛋白（AQP）8、AQP4及肠黏膜通透性相关蛋白ZO-1、Occludin的蛋白表达水平；蛋白免疫印迹法（Western blot）检测结肠组织中cAMP、PKA、CREB蛋白表达。

结果

与空白组比较，模型组大鼠腹泻评分及粪便含水率显著增高（

0.01），血浆二胺氧化酶（DAO）、血浆

-乳酸含量显著增高（

0.01），结肠ZO-1、Occludin、AQP8、AQP4、cAMP、PKA、CREB蛋白表达水平显著降低（

0.01）；与模型组比较，各给药组血浆二胺氧化酶（DAO）、

-乳酸含量显著降低（

0.01），结肠ZO-1、Occludin、AQP8、AQP4、cAMP、PKA、CREB蛋白表达水平显著升高（

0.01）。

结论

芍药汤减轻UC腹泻的机制可能是通过激活cAMP/PKA/CREB信号通路，上调AQPs的表达，增强肠上皮间紧密连接，进而改善结肠水液代谢和肠黏膜通透性。

Abstract

Objective

To investigate the role of cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP-response element binding protein （CREB） signaling pathway in water metabolism and intestinal epithelial permeability in ulcerative colitis （UC） and the intervention mechanism of Shaoyaotang based on the theory of large intestine governing fluids.

Method

Sixty male SD rats were divided into blank group， model group， mesalazine group （0.42 g·kg

-1

）， Shaoyaotang low-dose group （11.1 g·kg

-1

）， Shaoyaotang medium-dose group （22.2 g·kg

-1

） and Shaoyaotang high-dose group （44.4 g·kg

-1

）， with 10 in each group. The UC rat model of internal retention of dampness-heat was established by compound factors. The blank group and the model group were given normal saline （

）. The mesalazine group was given mesalazine （

）， and Shaoyaotang low-， medium- and high-dose groups were administrated with corresponding doses of Shaoyaotang （

）. The treatment lasted for 14 days. The diarrhea score and fecal moisture content of rats in each group were observed. The contents of diamine oxidase （DAO） and

-lactic acid in plasma were detected by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of aquaporin （AQP）8， AQP4， ZO-1 and Occludin in colon tissues were detected by immunohistochemistry， while those of cAMP， PKA and CREB in colon tissues were determined by Western blot.

Result

Compared with the normal group， the model group had elevated diarrhea score and fecal moisten content （

0.01）， increased contents of DAO and

-lactic acid in plasma （

0.01） and decreased protein expressions of ZO-1， Occludin， AQP8， AQP4， cAMP， PKA and CREB in colon （

0.01）. Compared with the conditions in the model group， the contents of DAO and

-lactic acid in plasma in each administration groups were lower （

0.01）， while the protein expressions of ZO-1， Occludin， AQP8， AQP4， cAMP， PKA and CREB in colon were higher （

0.01）.

Conclusion

Shaoyaotang alleviates the diarrhea in UC， probably through activating cAMP/PKA/CREB signaling pathway， up-regulating expressions of AQPs， enhancing tight junctions in intestinal epithelium and thus improving the water metabolism in colon and the intestinal mucosal permeability.

关键词

芍药汤溃疡性结肠炎环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应成分结合蛋白（cAMP/PKA/CREB）信号通路水液代谢

Keywords

Shaoyaotangulcerative colitiscyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP-response element binding protein （CREB） signaling pathwaywater metabolism

references

BAKER D M，FOLAN A M，LEE M J，et al.A systematic review and Meta-analysis of outcomes after elective surgery for ulcerative colitis［J］.Colorectal Dis，2021，23（1）：18-33.

KOBAYASHI T，SIEGMUND B，LE BERRE C，et al.Ulcerative colitis［J］.Nat Rev Dis Primers，2020，6（1）：74.

ROWAN C R，BOLAND K，HAREWOOD G C.Ustekinumab as induction and maintenance therapy for ulcerative colitis［J］.N Engl J Med，2020，382（1）：91.

WU D，YANG Z，ZHAO C，et al.Infliximab versus cyclosporine for severe ulcerative colitis refractory to steroids： A protocol for systematic review and meta-analysis［J］.Medicine （Baltimore），2018，97（41）：e12657.

WU B，TONG J，RAN Z.Tacrolimus therapy in steroid-refractory ulcerative colitis： A review［J］.Inflamm Bowel Dis，2020，26（1）：24-32.

LIU Y，WEI W，LIANG S，et al.Esculentoside A could attenuate apoptosis and inflammation in TNBS-induced ulcerative colitis via inhibiting the nuclear translocation of NF-κB［J］.Ann Transl Med，2022，10（14）：771.

SHI L，WANG J，YANG Q，et al.Effect of Yang-activating and stasis-eliminating decoction from traditional Chinese medicine on intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium［J］.J Tradit Chin Med，2017，37（4）：452-460.

SHANGZU Z，DINGXIONG X，CHENGJUN M，et al.Aquaporins： Important players in the cardiovascular pathophysiology［J］.Pharmacol Res，2022，183：106363.

雷超芳，翟昌明，马重阳，等.王庆国治疗溃疡性结肠炎活动期经验总结［J］.山东中医杂志，2019，38（9）：861-865.

吴东升，曹晖，张彧，等.芍药汤对溃疡性结肠炎大鼠肠黏膜免疫屏障的干预作用［J］.中国实验方剂学杂志，2019，25（9）：6-11.

曹晖，吴东升，张彧，等.芍药汤对溃疡性结肠炎大鼠结肠组织病理变化及免疫功能的影响［J］.中国中医药信息杂志，2019，26（6）：59-63.

曹晖，吴东升，张彧，等.基于高通量测序技术研究芍药汤对溃疡性结肠炎大鼠肠道菌群的影响［J］.中国中医药信息杂志，2021，28（1）：61-66.

吴东升，曹晖，张彧，等.芍药汤通过抑制HIF-1α调节Th17/Treg平衡治疗溃疡性结肠炎［J］.中国实验方剂学杂志，2021，27（16）：9-15.

徐敏，王凤仪，赵党生，等.芍药汤对湿热内蕴型溃疡性结肠炎大鼠TLR4，NF-κB p65和IL-6表达的调控作用［J］.中国实验方剂学杂志，2020，26（14）：53-58.

ZHANG D，YANG L，SU W，et al.Aquaporin-4 is downregulated in the basolateral membrane of ileum epithelial cells during enterotoxigenic escherichia coli-induced diarrhea in mice［J］.Front Microbiol，2017，8：2655.

隋楠，田振国，刘继东.基于大肠主津理论下助阳通便膏对便秘模型小鼠结肠组织中MUC2、AQP3的影响［J］.中华中医药学刊，2020，38（10）：40-43，后插7-7后插8.

ZHAO D Y，ZHANG W X，QI Q Q，et al.Brain-derived neurotrophic factor modulates intestinal barrier by inhibiting intestinal epithelial cells apoptosis in mice［J］.Physiol Res，2018，67（3）：475-485.

KUO W T，ODENWALD M A，TURNER J R，et al.Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival［J］.Ann N Y Acad Sci，2022，1514（1）：21-33.

SHI L，XUN W，PENG W，et al.Effect of the single and combined use of curcumin and piperine on growth performance， intestinal barrier function， and antioxidant capacity of weaned wuzhishan piglets［J］.Front Vet Sci，2020，7：418.

LIU S，QIU Y，GU F，et al.Niacin improves intestinal health through up-regulation of AQPs expression induced by GPR109A［J］.Int J Mol Sci，2022，23（15）：235.

甘江华，黄玙璠，彭代银，等.3种石斛对脾阴虚型大鼠便秘的治疗作用及其机制初步研究［J］.中国中药杂志，2019，44（12）：2600-2606.

吴璐，赖艳，王莹，等.高通量测序技术研究蚕沙对湿阻中焦证大鼠肠道菌群的影响［J］.中国中药杂志，2020，45（3）：623-630.

徐雯，王楠，丁浩然，等.广藿香对湿阻中焦证大鼠胃肠功能的影响［J］.中国中药杂志，2017，42（23）：4649-4655.

ZHAO G X，DONG P P，PENG R，et al.Expression， localization and possible functions of aquaporins 3 and 8 in rat digestive system［J］.Biotech Histochem，2016，91（4）：269-276.

彭强丽，张永会，杨丽娟.中药促进宫颈柱状上皮异位物理治疗后创面修复的临床观察及基于AQP2的机制探讨［J］.时珍国医国药，2017，28（7）：1683-1685.

汪刘华.AQP4在胃肠道的功能及与相关疾病关系的研究进展［J］.河北医科大学学报，2018，39（2）：244-248.

张馨心，周唯，陆金根，等.基于网络药理学探讨红萸饮治疗溃疡性结肠炎的分子机制［J］.世界中医药，2021，16（1）：52-62.

屈映，张书信，傅丽元，等.荆芥、防风对溃疡性结肠炎大鼠结肠黏膜AQP4和AQP8表达的影响［J］.中国中药杂志，2020，45（15）：3719-3725.

WU Z Y，YAO Y，HU R，et al.Cyclic adenosine monophosphate-protein kinase A signal pathway may be involved in pulmonary aquaporin-5 expression in ischemia/reperfusion rats following deep hypothermia cardiac arrest［J］.Genet Mol Res，2016，15（1）：15017377.

MENG Y，LI X，WANG X，et al.Network pharmacological prediction and molecular docking analysis of the combination of Atractylodes macrocephala Koidz. and Paeonia lactiflora Pall. in the treatment of functional constipation and its verification［J］.Animal Model Exp Med，2022，5（2）：120-132.

CHAO G，ZHANG S.Aquaporins 1， 3 and 8 expression and cytokines in irritable bowel syndrome rats' Colon via cAMP-PKA pathway［J］. Int J Clin Exp Pathol， 2018 ，11（8）：4117-4123.

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