The Effects Of Oxymatrine On β-arrestin1/2 Associated Signal Transduction Pathway In Rats With Ulcerative Colitis

Objective: To investigate the role ofβ-arrestin1/2 in the pathogenesis of ulcerative colitis and whether or not theβ2-adrenoceptor (β2AR)-β-arrestin2-NF-κB andδopioid receptor (DOR)-β-arrestin1-Bcl2 signal transduction pathway participate in the pathological process of ulcerative colitis. Furthermore to investigate oxymatrine attenuate the ulcerative colitis whether or not through its intervention effects on theβ-arrestin1/2 expression andβ2AR-β-arrestin2-NF-κB and DOR-β-arrestin1-Bcl2 signal transduction pathway.Methods: Forty SD rats were randomly divided into four groups which include normal control group, model group, mesalazine group and oxymatrine treatment group with 10 rats for each group. Uclerative colitis induced with TNBS was established in each group except the normal control group. After establishing the experiment colitis model, the rats of oxymatrine treatment group were intramuscularly injected with oxymatrine injections for 15 days, the rats of mesalazine group were lavaged with 3ml mesalazine solution for 15 days, the rats of normal control group and model group were lavaged with 3ml water for 15 days. Diarrhea and bloody stool as well as colonic histological changes in experiment rats were carefully observed. In 7th day two rats were randomly executed for observing the colonic histological changes in each group. In 16th day the experiment rats were executed and the expression ofβ2AR,β-arrestin2 and NF-κBp65 in experiment rats colon tissue and spleen lymphocytes and the expression of DOR,β-arrestin1 and Bcl2 in experiment rats colon tissue and spleen T lymphocytes were detected with immunohistochemistry and western immunoblotting techniques respectively. There are 2 rats died of lavage in normal control group, model group, mesalazine group respectively. Finally, 26 rats were included in statistics.Results: In contrast to normal control group the expression of NF-κBp65 were significantly increased (P <0.01) and the expression ofβ2AR andβ-arrestin2 were significantly decreased in model group (P <0.01). Compared with model group the expression of NF-κBp65 were significantly decreased (P <0.01) and the expression ofβ2AR andβ-arrestin2 were significantly increased in mesalazine group and oxymatrine treatment group (P <0.01).In contrast to normal control group the expression of DOR,β-arrestin1 and Bcl2 were significantly increased in model group (P <0.01). Compared with model group the expression of DOR,β-arrestin1 and Bcl2 were significantly decreased in mesalazine group and oxymatrine treatment group (P <0.01).Conclusion: The expression ofβ2AR andβ-arrestin2 decrease and the expression of NF-κB increase in ulcerative colitis. The impaired inhibition on activities of NF-κB is a possible pathogenesis of ulcerative colitis and theβ2AR-β-arrestin2-NF-κB signal transduction pathway participate in the pathologic course. Oxymatrine promote the expression ofβ2AR andβ-arrestin2 and inhibit the NF-κB activity to attenuate ulcerative colitis through regulating theβ2AR-β-arrestin2-NF-κB signal transduction pathway.The expression of DOR,β-arrestin1 and Bcl2 increase in ulcerative colitis and DOR-β-arrestin1-Bcl2 signal transduction pathway participates in the pathogenesis of ulcerative colitis. Oxymatrine inhibiting expression of DOR,β-arrestin1 and Bcl2 and intervening DOR-β-arrestin1-Bcl2 signal transduction is one of mechanisms of oxymatrine attenuating ulcerative colitis.