Research On The Anti-inflammation Effect And Mechanism Of CRYAB On Intestinal Inflammation And Clinical Study On Inflammatory Blowel Disease

Inflammatory bowel disease(IBD)is an inflammatory disease involving the entire colorectal mucosa.It is characterized by unknown etiology,recurrent episodes,and prolonged disease progression,which seriously affects the quality of life(QOL)of patients.IBD mainly includes ulcerative colitis(UC)and Crohn’s disease(CD).Although the treatment of IBD is mainly based on medical treatment,25-30% of patients still need surgical treatment due to drug treatment failure or complications.Therefore,it is particularly important to find new therapeutic targets for intestinal inflammation and to select appropriate surgical treatment of IBD properly.The study was conducted in two parts.The first part excavated the gene CRYAB,which plays an important role in regulating the development of intestinal inflammation.In the previous studies,CRYAB is thought to have anti-inflammatory effects in neuroinflammation.However,the role of CRYAB in the intestinal inflammation and its distribution in IBD patients remains unclear.We have demonstrated the low expression of CRYAB in inflammatory tissues through clinical samples of patients with IBD.Furthermore,we demonstrated in vitro that CRYAB not only inhibits the production of inflammatory cytokines,but also inhibits the effects of inflammatory cytokines.IKKβ activity assay and co-immunoprecipitation assays were performed to analyzd the mechanism by which CRYAB inhibits the inflammatory response,and it was found that CRYAB can inhibit activity of IKKβ by their interaction.Finally,we exogenously supplemented the purified TAT-CRYAB recombinant protein in dextran sulfate(DSS)-induced mice colitis model,it was found that supplementing the recombinant protein can significantly alleviate the intestinal inflammation and protect the mucosa barrier destruction caused by DSS.This part provides a new target and theoretical basis for the treatment of IBD.The second part is a multi-center long-term follow-up study that focuses on the clinical outcomes of UC complicated with colorectal strictures,the risk factors for UC malignant transformation and colorectal strictures.We found that disease duration of more than 5 years,moderated anemia and primary sclerosing cholangitis were contributing factors for the development of colorectal stricture.Earlier colonoscopic surveillance should be considered to prevent stricture formation and further malignant transformation.The third part is a clinical study to retrospectively analyze the surgical complications and long-term quality of life of patients with UC after ileal pouch–anal anastomosis(IPAA),to identify risk factors that affect the long-term QOL of patients,and to better improve the prognosis of patients.We found that early surgical complications,use of immunomodulators and older age at pouch surgery were independent factors of poor long-term QOL.Measuring surgical complications and functional long-term QOL are important in order to achieve an acceptable risk to benefit ratio for both surgeons and UC patients.Through the interconnected three parts of the study,this article from a new perspective to clarify the molecular mechanisms that may affect the development of IBD and provide new application prospects for the treatment of IBD,while further demonstrating the risk factors of colorectal stricture and effectiveness of IPAA surgery in patients with UC.