| Objective:To observe the inflammatory response induced by endoplasmic reticulum stress induced by Liancaoxieli capsule in rats,and explore a new way of prevention and treatment of ulcerative colitis,thus providing a new scientific basis for the treatment of UC.Methods:Forty male SD rats were fed for 1 week,10 rats were randomly selected as blank group,and the other 30 rats were randomly divided into model group,Liancaoxieli capsule group and mesalazine group by DSS modeling,with 10 rats in each group.The Liancaoxieli capsule group and mesalazine group were given drugs while modeling.After 7 days of intragastric administration,all rats were sacrificed,and blood samples from abdominal aorta and intestinal mucosa were collected for experiment and observed and recorded.Materials:The general state of the rats was observed,and the disease activity index(DAI)score was performed.After all the rats were sacrificed,the intestinal mucosa was collected and the length of the colon was recorded.The pathological images of the colon tissue were observed by HE staining under electron microscopy and the inflammation score was calculated.The serum LEVELS of IL-17,IFN-γ and IL-1β were detected by ELISA.Using Western The endoplasmic reticulum stress proteins GRP78 and CHOP and inflammatory related proteins Bcl-2,Bax,Capspase1,p-p65,p65,p-I кBα,IкBα,p-perk,PERK,p-EIF2 α,e IF2α,ATF4,p-IRE1 α,IRE1 were detected by blot method,x BP1 s,Cleaved ATF6,ATF6.Results:(1)Compared with the blank group,the food intake,hair gloss and body weight of rats in model group were gradually reduced.As time went by,naked blood stool was observed and death occurred in rats;Compared with model group,rats in Liancaoxieli capsule group had good mental state,increased food intake,increased body weight,bright and supple hair,no gross blood stool was observed,and fecal occult blood test was negative.(2)Compared with the blank group,the DAI score index of the model group was significantly increased(P<0.01),and the DAI score index of the mesalamine group and the Liancaoxieli capsule group was significantly decreased compared with the model group,with statistical significance(P<0.01).(3)Compared with model group,mesalamine group and Liancaoxieli capsule group could effectively reduce the levels of IL-17,IL-1β and IFN-γ in serum of rats(P<0.01).(4)Compared with model group,the length of colon in mesalamine group and Liancaoxieli capsule group was longer(P<0.01).(5)Compared with the model group,the mucosal structure of colon pouch in mesalazine group and Liancaoxieli capsule group was clear,and congestion,edema and ulcer were significantly improved.(6)DSS induced colonic inflammation in rats,and pathological score increased significantly;Liancaoxieli capsule and mesalazine effectively reduced the pathological score(P<0.01).(7)DSS induction can increase the expression of er stress marker protein GRP78 and CHOP protein in rat colon tissue;Liancaoxieli capsule and mesalazine can effectively reduce the expression level of er stress marker protein.(8)DSS induced apoptosis protein bcl-2 decreased,Bax increased,bcl-2 /Bax ratio decreased,and caspase-1 expression increased significantly.Compared with model group,The expression of Bcl-2 was increased,the expression of Bax was decreased,the ratio of Bcl-2 to Bax was increased(P<0.01),and the expression of Caspase-1 was significantly decreased(P<0.01).(9)Compared with the blank group,the expression of P-P65 and P-I кBα increased after DSS induction(P<0.01).The expression of P-P65 and P-IкBα was inhibited by Liancaoxieli capsule.(10)DSS induction can increase the expression of P-perk,P-EIF2 α,ATF4,P-IRE1 α,x BP1 s,Cleaved ATF6 proteins in rat er.Liancaoxieli capsule significantly reduced the expression of P-perk,P-EIF2 α,ATF4,P-IRE1 α,x BP1 s,Cleaved ATF6.Conclusion:(1)The experimental study showed that Liancaoxieli capsule can effectively relieve UC intestinal mucosa edema,bleeding,ulcer and other symptoms.(2)Liancaoxieli capsule can reduce the inflammatory response by reducing the expression of inflammatory factors IL-1β,IL-17,IFN-γ,and has a certain anti-inflammatory effect.(3)Liancaoxieli capsule inhibited er stress response by inhibiting the activation of THE PERK,IRE1 and ATF6 pathways of er signal.(4)Liancaoxieli capsule can protect intestinal mucosa by inhibiting cell apoptosis. |
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