Mechanism Of Curcumin Regulating Autophagy To Promote Mucosal Repair Of Ulcerative Colitis

Objective To observe the expression changes of Autophagy proteins Beclin1 and LC3II/I in colon tissue of mice with Ulcerative Colitis(UC)induced by Dextran Sodium Sulfate(DSS),and the possible mechanism of Curcumin regulating Beclin1 and LC3 in intestinal mucosal repair in mice with Ulcerative Colitis.Methods Sixty SPF and male BALB/C mice were selected.The body weight was(18±2.5)g,and the age of rats was 6-8 weeks.They were randomly divided into normal control group,model control group,curcumin gavage group and mesalazine group.There were 15 rats in each group.There was no significant difference in body mass between the groups after randomization.After 7 days of adaptive feeding,in addition to the normal control group,the model control group,the curcumin gavage group and the mesalazine gavage group all used the DSS method to manufacture the UC model.From the first day of modeling,the mice in the curcumin gavage group were given curcumin by intragastric administration.The mice in the mesalazine group were given mesalazine suspension 500mg/kg,and the mice in the model control group and the normal control group were given normal saline.From the date of modeling,the model of the mouse model was evaluated by the Cooper method.The traits of the stool,blood in the stool,changes in spirit and body weight were observed every day.The Disease Activity Index of the four groups of mice was recorded and calculated(DAI),each group of mice was treated continuously for21 days,and the mice were sacrificed on the 22 nd day,and colon tissue samples were taken for testing.The pathological damage of colon,Immunofluorescence and Western Blot were used to detect the expression of Beclin1 and LC3II/I in mouse colon tissue.Results(1)After the model was prepared,the mice in the model control group had less activity,poor mentality,decreased body weight,no stool formation,mucuspus and bloody stools in the eyes,and stool characteristics and blood in the stool in the curcumin group compared with the model control group,but still a small amount of pus and bloody stools;the mesalazine group with a small amount of diarrhea,mucus,black stools,bloody stools.The DAI score showed that the model control group began to develop colonic inflammatory symptoms on the second day and gradually began to aggravate,suggesting that the DSS mice were successfully modeled;(2)After successful modeling,HE staining showed that the histopathological damage score of the mice was in curcumin.The gavage group(2.23±0.10)was significantly higher than the normal control group(0.07±0.05)(P<0.01),which was significantly lower than the model control group(3.90±0.07)(P<0.01).(3)Immunofluorescence staining showed the expression of Beclin1 and LC3 in the curcumin group was significantly higher than that in the normal control group(0.74±0.02 vs.0.17±0.11,P<0.01;0.77±0.06 vs.0.26±0.02,P<0.01),but lower than the model control group(0.74±0.02 vs 0.89±0.02,P<0.05;0.77±0.06 vs.1.06±0.02,P<0.05);(4)Western Bolt suggested that Beclin1 and LC3II/I were higher in the curcumin gavage group than in the normal control group(0.27±0.02 vs.0.11±0.01,P<0.01;1.64±0.05 vs.0.55±0.07,P<0.01),but lower than the model control group(0.27±0.02 vs.0.36±0.01,P<0.05;1.64±0.05 vs 1.87±0.04,P < 0.05).Conclusions(1)Overexpression of Beclin 1 and LC3 in colitis mucosa may lead to the pathogenesis of Ulcerative Colitis;(2)Curcumin can improve and repair intestinal mucosal damage by down-regulating the expression of related autophagy genes.