Role of β2-Adrenoceptor-β-Arrestin2-Nuclear Factor-κB Signal Transduction Pathway and Intervention Effects of Oxymatrine in Ulcerative Colitis

Objective: To investigate the beta 2-adrenoceptor (beta 2AR)-beta-arrestin2-nuclear factor-kappa B (NF-kappa B) signal transduction pathway and the intervention effects of oxymatrine in a rat model of ulcerative colitis. Methods: Forty SD rats were randomly divided into four groups, which included the normal control group, the model group, the mesalazine group and the oxymatrine treatment group, with 10 rats per group. Experimental colitis induced with trinitrobenzene sulfonic acid (TNBS) was established in each group except the normal control group. The rats in the oxymatrine treatment group were treated with intramuscular injection of oxymatrine 63 mg/(kg.d) for 15 days and the rats in the mesalazine group were treated with mesalazine solution 0.5 g/(kg.d) by gastric lavage for 15 days. The rats in the normal control group and model group were treated with 3 mL water by gastric lavage for 15 days. Diarrhea and bloody stool were carefully observed. Histological changes in colonic tissue were examined on day 7 in 2 rats per group that were randomly selected. The expression of beta 2AR, beta-arrestin2 and NF-kappa Bp65 in colon tissue and spleen lymphocytes were detected with immunohistochemistry and Western immunoblotting techniques on day 16 after fasting for 24 h. Six rats died of lavage with 2 each in the normal control, the model group and the mesalazine group; and were not included in the analysis. Results: The rats in the model group suffered from looser stool and bloody purulent stool after modeling. But in the oxymatrine and mesalazine groups, looser stool and bloody purulent stool reduced after treatment. And the colonic wall in the model group was thickened and the colon length shortened. The colon mucosa was congested in multiple areas with edema, erosion, superficial or linear ulcer and scar formation, while the intestinal mucosa injury reduced in the mesalazine and oxymatrine groups (P<0.01). In colonic mucosa and in spleen lymphocytes, compared with the normal control group, the expression of NF-kappa Bp65 were significantly increased (P<0.01) in the model group while the expressions of beta 2AR and beta-arrestin2 were significantly decreased (P<0.01). Compared with the model group, the expression of NF-kappa Bp65 was significantly decreased in the mesalazine group (P<0.01) and oxymatrine treatment group (P<0.01) while the expressions of beta 2AR and beta-arrestin2 were significantly increased (P<0.01). There were no statistically significant differences in the expression of beta 2AR, beta-arrestin2 and NF-kappa Bp65 between the mesalazine group and oxymatrine group (P>0.05). Conclusions: The beta 2AR-beta-arrestin2-NF-kappa B signal transduction pathway participated in the pathologic course of ulcerative colitis. Oxymatrine attenuated ulcerative colitis through regulating the beta 2AR-beta-arrestin2-NF-kappa B signal transduction pathway.