title: Role of β2-adrenoceptor-β-arrestin2-nuclear factor-κB signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis.
abstract: OBJECTIVE
  To investigate the β2-adrenoceptor (β2AR)-β-arrestin2-nuclear factor-κB (NF-κB) 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 β2AR, β-arrestin2 and NF-κB p65 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-κBp65 were significantly increased (P<0.01) in the model group while the expressions of β 2AR and β-arrestin2 were significantly decreased (P<0.01). Compared with the model group, the expression of NF-κ Bp65 was significantly decreased in the mesalazine group (P<0.01) and oxymatrine treatment group (P<0.01) while the expressions of β2AR and β-arrestin2 were significantly increased (P<0.01). There were no statistically significant differences in the expression of β2AR, β-arrestin2 and NF-κBp65 between the mesalazine group and oxymatrine group (P>0.05).
  
  
  CONCLUSIONS
  The β2AR-β-arrestin2-NF-κB signal transduction pathway participated in the pathologic course of ulcerative colitis. Oxymatrine attenuated ulcerative colitis through regulating the β2AR-β-arrestin2-NF-κB signal transduction pathway.
authors: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Tecnology, Wuhan 430022, China.
authors: Heng
authors: H
authors: Fan
authors: Yi
authors: Y
authors: Liao
authors: Qing
authors: Q
authors: Tang
authors: Xiao-Yan
authors: XY
authors: Chen
authors: Li-Juan
authors: LJ
authors: Zhang
authors: Xing-Xing
authors: XX
authors: Liu
authors: Min
authors: M
authors: Zhong
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013154:Spleen / Q000473:pathology; D000071557:beta-Arrestins; D000093842:Matrines
chemical_list: D000470:Alkaloids; D019390:Arrestins; D016328:NF-kappa B; D011807:Quinolizines; D018343:Receptors, Adrenergic, beta-2; D000071557:beta-Arrestins; C037573:oxymatrine; D000093842:Matrines