Experimental Study on Bortezomib for Treatment of Ulcerative Colitis
10.3969/j.issn.1008-7125.2017.07.004
- VernacularTitle:硼替佐米在溃疡性结肠炎中治疗作用的实验研究
- Author:
Lihong HU
;
Qing LI
;
Bo QU
- Keywords:
Bortezomib;
NF-kappa B;
Colitis;
Ulcerative;
Therapy;
Mice;
Inbred MALB C
- From:Chinese Journal of Gastroenterology
2017;22(7):402-406
- CountryChina
- Language:Chinese
-
Abstract:
Background:The efficacy of traditional medicine on ulcerative colitis (UC) is often unsatisfactory, hence development of drug based on the pathogenic mechanism of UC becomes a hot topic in the research of UC.It has been revealed in recent studies that activation of nuclear factor-κB (NF-κB) is implicated as a key regulator in the immune and inflammatory responses in UC.Aims:To explore whether bortezomib, a potent proteasome inhibitor that inhibits NF-κB activation can be used for treatment of UC.Methods:Thirty-two BALB/c mice were used to induce acute experimental colitis by drinking 3%dextran sulfate sodium (DSS) freely for 7 days, and then randomly allocated into four groups injected intraperitoneally with 0.2 (low-dose group), 0.6 (medium-dose group), 1.0 mg/kg (high-dose group) bortezomib and normal saline (model control group), respectively.On the 7th day after treatment, the disease activity index (DAI) and histopathological change of colonic tissue were observed;the colitis-related parameters including peripheral blood hemoglobin (Hb), C-reactive protein (CRP) and colonic myeloperoxidase (MPO) activity were measured, and the nuclear translocation of NF-κB was assessed by electrophoretic mobility shift assay.Results:Compared with the model control group, the DAI, CRP, MPO activity, and injury score of colonic tissue were decreased gradually, and the Hb was increased gradually in mice treated with low-, medium-and high-dose bortezomib (P all <0.05).The efficacy of medium-and high-dose bortezomib was notable.In mice treated with medium-and high-dose bortezomib, nuclear translocation of NF-κB was inhibited obviously.Conclusions:Bortezomib can modulate the colonic inflammation in mice with experimental colitis by inhibiting NF-κB activation and subsequently improving the clinical manifestations, colitis-related parameters and tissue damage.Increasing the dosage of bortezomib in a safety range may enhance the treatment response.
