Dajianzhong decoction in treating visceral pain of irritable bowel syndrome based on ERK 1/2/nuclear factor κB signal pathway

WU Jing; YANG Sha-Sha

doi:10.16098/j.issn.0529-1356.2022.03.002

PDF(2533 KB)

Acta Anatomica Sinica ›› 2022, Vol. 53 ›› Issue (3) : 281-287. DOI: 10.16098/j.issn.0529-1356.2022.03.002

Dajianzhong decoction in treating visceral pain of irritable bowel syndrome based on ERK 1/2/nuclear factor κB signal pathway

WU Jing¹ YANG Sha-sha^2* YANG Yi¹ LI Yao-feng¹ WANG Jun-xia¹ CHEN Xiang-yun¹

Author information +

History +

Abstract

Objective To investigate whether Dajianzhong decoction can treat visceral pain of irritable bowel syndrome (IBS) by interfering with ERK1/2/nuclear factor κB (NF-κB )pathway and its downstream molecules. Methods The IBS visceral pain rat model was prepared by method such as mother-infant separation, acetic acid enema, and intraperitoneal injection of chicken ovalbumin. Rats were randomly divided into normal control group (normal saline), model group (normal saline), Dajianzhong decoction (10.8g/kg) treatment group, and the control group of pinaverium bromide (45 mg/kg). Eight rats in each group were given intragastrically for 14 days. To evaluate the visceral sensitivity of rats, abdominal withdrawal reaction (AWR) was used; the expression of ERK1/2 mRNA, NF-κB mRNA, cyclooxygenase-2 (COX-2 )mRNA, and matrix metalloproteinase 9 (MMP-9) mRNA in colon tissue of rats in each group were detected by Real-time PCR; Immunohistochemistry staining method was used to detect the expression of NF-κB and COX-2 in the colon tissue of each group. Results Compared with the normal rats, AWR scores of model rats increased significantly at 60, 40 and 20 mmHg pressure (P<0.05, P<0.01), ERK1/2, NF-κB, COX-2 and MMP-9 expression increased significantly (P<0.05); Compared with the model rats, the AWR score of the Dajianzhong decoction group (60, 40 and 20 mmHg pressure) decreased significantly (P<0.05, P<0.01), ERK1/2, NF-κB, COX-2 and MMP-9 decreased significantly (P<0.05); Compared with the pinaverium bromide control group, ERK1/2, NF-κB, COX-2 and MMP-9 expression in the Dajianzhong decoction treatment group had no statistical difference (P>0.05). Conclusion Dajianzhong decoction can play a role in treating visceral pain of irritable bowel syndrome (IBS) by interfering ERK1/2/NF-κB pathway and its downstream molecules.

Key words

Visceral pain / Extracellular signal-regulated kinase 1/2 / Dajianzhong decoction / Real-time PCR / Immunohistochemistry / Rat

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

WU Jing YANG Sha-sha YANG Yi LI Yao-feng WANG Jun-xia CHEN Xiang-yun. Dajianzhong decoction in treating visceral pain of irritable bowel syndrome based on ERK 1/2/nuclear factor κB signal pathway[J]. Acta Anatomica Sinica. 2022, 53(3): 281-287 https://doi.org/10.16098/j.issn.0529-1356.2022.03.002

References

［1］Cai LK，Peng ZhY，Huang Sh，et al.Meta-analysis of therapeutic efficacy and safety of mirtazapine combined with selective calcium channel blocker in the treatment of irritable bowel syndrome［J］.China Pharmacy，2019，30（18）：2563-2570. (in Chinese)

蔡林坤，彭卓嵛，黄适，等.米氮平联合选择性钙通道拮抗剂治疗肠易激综合征有效性与安全性的Meta分析［J］.中国药房，2019，30（18）：2563-2570.

［2］Wu J，Wang H，Wang JX，et al.Effects of Dajianzhong decoction on serum IL-6，TNF-α and IRAK-4 mRNA expression in colon mucosa of chronic inflammatory visceral pain model rats［J］.Journal of Traditional Chinese Medicine, 2018,59(18):1592-1596.(in Chinese)

武静,王慧,王俊霞,等.大建中汤对慢性炎性内脏痛模型大鼠血清IL-6、TNF-α含量及结肠黏膜IRAK-4 mRNA表达的影响［J］.中医杂志,2018,59(18):1592-1596.

［3］Kavalali ET, Monteggia LM. The ketamine metabolite 2R,6R-hydroxynorketamine blocks NMDA receptors and impacts downstream signaling linked to antidepressant effects［J］. Neuropsychopharmacology,2018, 43(1): 221-222.

［4］Jin X，Shi YSh，Yang YY, et al.Research progress of mechanisms of hyperalgesia induced by extracellular signal-regulated kinase1/2 ［J］.Medical Recapitulate,2019,25(2):247-251, 257.(in Chinese)

金旭,石翊飒,杨园园,等.细胞外信号调节激酶1/2诱导痛觉过敏机制的研究进展［J］.医学综述,2019,25(2):247-251, 257.

［5］Zhang N，Cui J，Feng L, et al.Clinical study on the effect of electroacupuncture at “Neiguan”and “Tongli”combined with basic drugs on serum MMP-9 and TIMP-1 in patients with chronic stable angina pectoris［J］.Journal of Basic Chinese Medicine,2018, 24(5):648-650,661.(in Chinese)

张宁,崔瑾,冯麟,等.电针“内关”“通里”穴联合基础药物对慢性稳定性心绞痛患者血清MMP-9、TIMP-1影响的临床研究［J］. 基础中医杂志,2018, 24(5):648-650+661.

［6］Niu YX, Sun B, Bai F, et al.Clinical application and modern research progress of Dajianzhong decoction［J］.Chinese Journal of Pharmacology and Toxicology,2019,33(9):715-716.(in Chinese)

牛艺璇,孙波,白埔,等.大建中汤的临床应用及现代研究进展［J］.中国药理学与毒理学杂志,2019,33(9):715-716.

［7］Liu XG，Zhou LJ.Long-term potentiation at spinal C-fiber synapses: a target for pathological pain［J］.Curr Pharm Des，2015，21(7):895-905.

［8］Mikuzuki L, Saito H, Katagiri A, et al. Phenotypic change in trigeminal ganglion neurons associated with satellite cell activation via extracellular signal-regulated kinase phosphorylation is involved in lingual neuropathic pain［J］. Eur J Neurosci, 2017,46(6):2190-2202.

［9］Juan YS, Lee YL, Long CY, et al. Translocation of NF-κB and expression of cyclooxygenase-2 are enhanced by ketamine-induced ulcerative cystitis in rat bladder［J］. Am J Pathol, 2015, 185（8）:2269-2285.

［10］Cheng Zh, Zhang WY. Matrix metalloproteinases and their tissue inhibitors in inflammatory bowel disease［J］.Practical Journal of Clinical Medicine，2008，5(6)：128-130. (in Chinese)

程倬，张文远.基质金属蛋白酶及其抑制物与炎症性肠病［J］.实用医院临床杂志，2008，5(6)：128-130.

［11］Schoonbroodt S, Piette J. Oxidative stress interference with the nuclear factor-kappa B activation pathways ［J］. Biochem Pharmacol, 2000, 60(8): 1075-1083.

［12］Ishinaga H, Jono H, Lim JH, et al. TGF-beta induces p65 acetylation to enhance bacteria-induced NF-kappaB activation［J］. EMBO J, 2007, 26(4): 1150-1162.

［13］Kavalali ET, Monteggia LM. The ketamine metabolite 2R,6R-hydroxynorketamine blocks NMDA receptors and impacts downstream signaling linked to antidepressant effects［J］. Neuropsychopharmacology, 2018, 43(1): 221-222.

［14］Liu WT，Han Y，Liu YP，et al.Spinal matrix metalloproteinase-9 contributes to physical dependence on morphine in mice［J］.J Neurosci，2010，30（22）：7613-7623.

［15］Kawasaki Y，Xu ZZ，Wang X，et al.Distinct roles of matrix metalloproteases in the early-and late-phase development of neuropathic pain［J］.Nat Med，2008，14 （3）：331-336.

［16］Ling QM, Han F. Effect of Changkang granules on MMP-3 and MMP-9 levels in colonic tissue of rats with ulcerative colitis［J］. Chinese Journal of Gerontology，2012，32(9)：1886-1887. (in Chinese)

刘青梅，韩辅.肠康颗粒对溃疡性结肠炎大鼠结肠组织MMP-3，MMP-9水平的影响［J］.中国老年学杂志，2012，32(9):1886-1887.

［17］Aquino AB, CavalcanteSilva LH, Matta CB，et al. The antinociceptive and anti-inflammatory activities of aspidosperma tomentosum （apocynaceae ）［J］. Scientific World Journal，2013，2013：218627.

［18］Ulmann L，Hirbec H，Rassendren F.P2X4 receptors mediate PGE 2 release by tissue-resident macrophages and initiate inflammatory pain［J］.EMBO J，2010，29（4）：2290-2300.

［19］Jiang HL，YU X，Ren XJ，et al. Electroacupuncture alters pain-related behaviors and expression of spinal prostaglandin E2 in a rat model of neuropathic pain［J］. J Tradit Chin Med，2016，36（1）：85-91.