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Summary Of Experience And Potential Mechanism Research Of Huangkui Lianchang Decoction In Treatment Of Ulcerative Colitis

Posted on:2021-03-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z Q HeFull Text:PDF
GTID:1364330605955703Subject:Chinese traditional surgery
Abstract/Summary:PDF Full Text Request
Ulcerative colitis is a chronic inflammatory disease affecting the colon,and its incidence is rising worldwide.The pathogenesis is multifactorial,involving genetic predisposition,epithelial barrier defects,dysregulated immune responses,and environmental factors.Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon.Ulcerative colitis usually presents with abdominal pain,bloody diarrhea and is diagnosed by colonoscopy and histological findings.At present,the variety of drugs for treating UC can alleviate intestinal inflammation,and long-term medication needs to be maintained.These drugs are expensive,and the side effects of long-term use reduce the quality of life and satisfaction of patients.Therefore,looking for a drug with the characteristics of "simple,convenient,tested,and inexpensive" with small side effects is urgent.Clinical application of traditional Chinese medicine for the treatment of ulcerative colitis is increasingly widespread.Huangkui Lianchang Decoction which is useful in clinical enema alone or in combination with oral medicines,is the experience of Professor Chen Yugen,the mechanism is unclear.This study objectively evaluated the efficacy of Huangkui Lianchang Decoction in the treatment of ulcerative colitis and clarified the possible mechanism to provide a basis for the promotion of the famous Chinese medicine prescription.This paper is divided into two parts:literature research and experimental research.Literature Research1 From the perspective of the Chinese Medicine,the disease name,etiology,pathogenesis,treatment and prescription of ulcerative colitis are systematically reviewed.2 From the perspective of the Modern Medicine,the pathogenesis,drug treatment,and surgical treatment of ulcerative colitis are systematically described.3 Review the progress of traditional chinese medicine enema in the treatment of ulcerative colitis,summary Professor Chen Yugen's experience in treating ulcerative colitis.4 Explain the research progress of experimental chemical modeling methods for animals of ulcerative colitis.Experimental Study of Huangkui Lianchang Decoction in Treating Ulcerative Colitis Background and Objective:Huangkui Lianchang decoction(HLD)is an effective traditional Chinese medicinal compound used in the treatment of UC.HLD has good effects in the clinic,but the mechanism by which HLD acts is unclear.The nuclear factor kappa beta(NF-?B)signaling pathway,IL-6/STAT3 signaling pathway and IL-23/IL-17 axis play an important role in ulcerative colitis(UC).This study aims to reveal the exact molecular mechanism of HLD in the treatment of UC.Methods:Mouse ulcerative colitis was induced by dextran sulfate sodium(DSS)and treated with HLD.Intestinal damage was assessed by disease activity index(DAI)and histological scores.Interleukin(IL)-6,tumor necrosis factor(TNF)-?,IL-1?,IL-23 and IL-17 levels were detected in colon tissue using ELISA.Myeloperoxidase(MPO)and superoxide dismutase(SOD)activities in the colonic mucosa were measured.The mRNA levels of IL-6,inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),IL-23,IL-17 and glycoprotein 130(gp130)content in the colon were determined by real-time quantitative polymerase chain reaction(qPCR).The expression of I?B?,p-I?B?,retinoic acid receptor-associated orphan nuclear receptor(RORy t),signal transducer and activator of transcription 3(STAT3)and p-STAT3 in the colon was measured by Western blot.Immunohistochemistry was used to determine the protein expression of NF-?B,STAT3 and p-STAT3 in colon tissue.Results:After treatment with HLD,the DAI scores,macroscopic lesion scores and histological scores decreased.And the levels of inflammatory cytokines related to the NF-?B signaling pathway,such as TNF-?,and IL-1?,as well as those of iNOS,COX-2,NF-?B,I?B? and p-I?B? were reduced;IL-6/STAT3 signaling pathways and IL-23/IL-17 inflammatory axis-associated inflammatory factors,such as IL-6,IL-23,IL-17,gp130,ROR? t,p-STAT3 and STAT3 were significantly reduced.At the same time,colonic pathological damage was alleviated,and the MPO and SOD activities decreased.Immunohistochemistry and western blot confirmed that HLD can inhibit the NF-?B signaling pathway and IL-6/STAT3 signaling pathway in DSS-induced ulcerative colitis.Conclusion:HLD can alleviate the inflammation caused by ulcerative colitis.In particular,high doses of HLD can significantly alleviate intestinal inflammation and have comparable efficacy to mesalazine.We propose that the anti-inflammatory activity of HLD on DSS-induced colitis in mice may involve the inhibition of the NF-?B pathway,IL-6/STAT3 signaling pathway and IL-23/IL-17 axis.
Keywords/Search Tags:Huangkui Lianchang decoction, ulcerative colitis, NF-?B pathway, IL-6/STAT3 signaling pathway, IL-23/IL-17 axis, mesalazine
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