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Resveratrol Effects On The SIRT1/mTOR Signaling Pathway In Colonic Epithelium Of Mice With Ulcerative Colitis

Posted on:2022-01-09Degree:MasterType:Thesis
Country:ChinaCandidate:J H WangFull Text:PDF
GTID:2504306566480694Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Purpose In recent years,studies by a large number of scholars have shown that resveratrol,as a purified botanical antitoxin,exists in a variety of plants in nature,especially polygonum cuspidatum and grapes.It is derived from nature and has a relatively high content.Low,a natural non-flavonoid polyphenol extract that requires multiple transformations.Resveratrol is extracted through a variety of methods and then made into medicines,which is often low in the human body,but It can effectively prevent oxidative free radicals,effectively prolong the average life span of people,effectively prevent the aggregation of platelets,improve the general state of the body,improve the body’s immunity,improve the body’s anti-tumor ability,and the aggregation of anti-inflammatory factors and protect the heart Vascular system.This study makes full use of low,medium and high doses of resveratrol through diet gavage to intervene experimental ulcerative colitis mouse models and other means,intervening through free drinking of dextran sodium sulfate liquid to induce intestinal tract In the inflammatory response of ulcerative colitis model mice,it is possible to prove the potential regulation ability of the important node protein in the signaling pathway of the silent information regulator 1 mammalian target of rapamycin and the potential regulation of autophagy and immune response.The results can prove that it provides a new and effective therapeutic potential target for the clinical application of resveratrol in ulcerative colitis.Methods BALB/c mice were randomly divided into different groups by reference weight,such as: control(CON)group,model(DSS)group,resveratrol control(RES)group,resveratrol was divided into low(RLD;10 mg/kg),medium(RMD;50 mg/kg),and high(RHD;100 mg/kg)three dose groups;all groups remain as they are,except for the CON and RES groups.Each group drank 3.5% DSS solution to make the model,so as to ensure that the preparation of the model is relatively successful;three concentrations of resveratrol were given to the mice with corresponding drugs,and the different doses of drugs were based on different body surface areas.The mice are sure,only in this way can it be guaranteed to test whether resveratrol is really useful;among them,the mice in the CON and DSS groups were gavaged with normal saline to facilitate the control of experimental results.After gavage with normal saline,the mice were put Enter the cage for comfort to avoid further damage;record the physical signs of different groups of mice at fixed intervals,and calculate the disease activity index.Using a variety of research methods and programs including Western blotting and real-time fluorescent quantitative polymerase chain reaction,the expression of SIRT1,mTOR,LC3Ⅱ/Ⅰ,Beclin-1,Atg12 m RNA and protein in mouse colon tissue And its expression in the intestinal mucosal epithelium.Results Resveratrol,as a SIRT1 agonist,significantly promoted the expression of the SIRT1/mTOR signaling pathway.Different doses of resveratrol activated the SIRT1/mTOR signaling pathway to varying degrees.As we can see,the body weight,physical activity,food intake,ability to respond to external stimuli and DAI scores of the DSS group mice were much higher than those of the CON group(P<0.05).From the experimental results,After freely drinking DSS solution,the mice had clinical manifestations of UC,the mice had pus and blood,and the colon tissue of the mice was observed under the microscope,and the intestinal wall properties were changed;and the mice were induced by DSS,the expression of SIRT1 and mTOR Significant decrease(P<0.05),which may also indicate from another aspect that DSS has an inhibitory effect on the SIRT1/mTOR pathway in mice;the content of TNF-α,IL-1β,and IL-6 in the mouse body increased,indicating that The mouse is now in a state of fever(P<0.05),and at the same time the IL-10 content is reduced(P<0.05),indicating that DSS-induced UC mice have increased the content of inflammation-related factors and reduced the number of anti-inflammatory-related factors;Autophagy-related proteins in the mouse body: LC3Ⅱ/Ⅰ,Beclin-1,Atg 12 expression increased significantly(P<0.05),indicating that resveratrol may have a significant impact on the basic functions of autophagy in mice;The ratio of CD4+T in the mesenteric lymph nodes of mice decreased,and the differentiation of Th began to produce a variety of different places(P<0.05),indicating that the immune function of DSS-induced UC mice was affected;and the CON group In comparison,the expression of SIRT1 and mTOR in the body of the resveratrol group mice increased,which can indicate that this pathway in the mice has been activated and excited to a certain extent(P<0.05),indicating that resveratrol It is a natural SIRT1/mTOR pathway agonist;compared with the DSS group,the disease activity index scores of mice in each group of resveratrol decreased(P<0.05),and the disease activity index truly reflects the different periods in the mice Different inflammatory states;the ratio of CD4+T in MLN increased(P<0.05),indicating that resveratrol has improved immunity and expression of inflammation-related factors,and autophagy in DSS-induced UC mice.ease.Conclusion Resveratrol can significantly improve the symptoms of UC mice,at the same time improve the general condition of mice,and improve the quality of life;resveratrol may stimulate the SIRT1 protein in the colon tissue of mice to promote the expression of SIRT1/mTOR signaling pathway.Thereby reducing autophagy in mouse colon tissue,improving the inflammatory environment of the intestine,reducing the accumulation of inflammation-related factors,so as to achieve the purpose of treating UC.The experimental results also show that different doses of resveratrol can affect UC mice The improvement and therapeutic effect of the drug are also different,basically showing a dose-dependent change.
Keywords/Search Tags:resveratrol, ulcerative colitis, SIRT1/mTOR signaling pathway, autophagy
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