大鼠急性肠炎早期核因子-κB活化以及吡咯烷二硫氨基甲酸的抗炎作用

Activation of NF-κB and anti-inflammation mechanism of pyrrolidine dithiocarb amate in rats with acute colitis

目的 :探讨NF κB在三硝基苯磺酸 (TNBS) 乙醇所致的大鼠结肠炎的早期活化情况 ;吡咯烷二硫氨基甲酸 (PDTC)在该模型中的抗炎作用。方法 :TNBS 乙醇灌肠建立大鼠急性结肠炎的模型 ,造模前30min经腹腔分别注射不同剂量的PDTC(1 0 ,2 5 ,50 ,1 0 0mg·kg- 1) ,设立空白对照 ,模型对照组。造模后 4h处死大鼠 ,观察结肠大体形态、湿干比及组织学改变 ,EMSA法测定NF κB的DNA结合活性 ,并检测组织中MPO、SOD、MDA变化。结果 :TNBS 乙醇造模后大鼠结肠组织中NF κB早期活化 ,PDTC能减轻TNBS 乙醇所致炎症 ,湿干比下降 ,组织学评分减少 ,MPO ,MDA值下降 ,与所用剂量正相关 ,但上述作用不通过阻断NF κB途径。结论 :NF κB在TN BS 乙醇结肠炎早期迅速活化 ,可能是机体一种早期抗损伤的自我防御事件 ,PDTC能够在早期减轻TN BS

AIM: To investigate DNA-binding activity of nuclear factor ka ppa B (NF-κB) and pyrrolidine dithiocarbamate (PDTC) anti-inflammation effect and mechanism in trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats. METHODS: Acute colitis was induced by instilling TNBS/ ethanol into the lumen of the rat colon. Rats were randomized into PDTC-treat g roup (including group P10,P25,P50,P100), TNBS/ethanol group and normal control g roup. The rats in PDTC-treated group were injected intraperitoneally with PDTC at the dosages of 10, 25, 50, and 100 mg·kg -1 , respectively. Rats wer e killed at 4 h after enema. Colonic inflammation, the ratio of wet/dry weig ht and MPO, SOD, and MDA activity were detected. DNA-binding activity of NF-κ B was assessed by EMSA. RESULTS: NF-κB activity in colon homog enate was increased markedly at acute colitis in rats. PDTC attenuates the devel opment of rat colonic inflammation but not by reducing the NF-κB activity. CONCLUSION: NF-κB is activated in rats with acute colitis, which may be a mechanism of self-protection. PDTC can attenuate the development of in flammation.