论文部分内容阅读
目的:观察p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)特异性抑制剂SB203580对大鼠实验性结肠炎(ulcerative colitis,UC)外周血淋巴细胞(peripheral blood lymphocyte,PBL)凋亡及相关调控蛋白的影响,探讨P38MAPK通路在UC中的可能作用及机制.方法:45只健康SD大鼠随机均分为正常对照组、结肠炎模型组、SB203580组.模型组及SB203580组以三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)制备大鼠溃疡性结肠炎模型,正常对照组给予等量0.9%生理盐水灌肠,SB203580组于造模完成后给予1 mg/(kg·d)SB203580腹腔注射.流式细胞仪技术检测PBL凋亡率及Bcl-2表达率,免疫组织化学方法检测活化转录因子-2(phosphoractivating transcription factor 2,p-ATF2)表达;同时观察大鼠疾病活动指数(disease activity index,DAI)、肠道大体形态及组织学评分情况;分析p-ATF2水平与PBL凋亡率及Bcl-2达率的相关关系.结果:与正常组相比,模型组大鼠肠组织磷酸化p-ATF2及PBL中Bcl-2阳性表达显著增高(43.40%±2.67%vs 7.45%±1.26%,38.60%±3.53%vs 13.70%±2.45%,P<0.01),PBL凋亡率明显降低(27.70%±3.02%vs 58.70%±3.09%,P<0.01);SB203580组p-ATF2、Bcl-2阳性表达率较模型组明显下降(20.70%±2.79%,20.30%±2.87%,P<0.01),PBL凋亡率较模型组明显上升(46.60%±4.14%,P<0.01).大鼠DAI及肠道大体形态、组织学评分模型组明显高于正常组(2.42±0.30 vs 0.28±0.29,5.42±0.30 vs 0.30±0.48,3.29±0.26 vs 0.05±0.20,P<0.01),SB203580组较模型组明显下降(1.24±0.17,3.30±0.22,1.10±0.74,P<0.01).结论:P38MAPK抑制剂SB203580通过下调p-ATF2活性及Bcl-2表达,促进PBL的凋亡减轻UC大鼠肠道炎症损伤,对UC具有保护作用.
AIM: To observe the apoptosis of peripheral blood lymphocytes (PBL) induced by p38 mitogen-activated protein kinase (MAPK), a specific inhibitor of SB203580, in rats with ulcerative colitis (UC) And related regulatory proteins, and explore the possible role of P38MAPK pathway in UC.Methods: Forty-five healthy SD rats were randomly divided into normal control group, colitis model group and SB203580 group.The model group and SB203580 group were divided into three groups The rat model of ulcerative colitis was prepared by using 2,4,6-trinitrobenzene sulfonic acid (TNBS). The normal control group was given 0.9% physiological saline enema, while the SB203580 group was given 1 mg / (kg · d) SB203580 intraperitoneal injection.Flow cytometry was used to detect the apoptosis rate of PBL and the expression of Bcl-2, and the expression of p-ATF2 was detected by immunohistochemistry The pathological index (DAI), gross gut morphology and histological score of rats were analyzed, and the correlation between the level of p-ATF2 and the rate of apoptosis of PBL and the rate of Bcl-2 was analyzed.Results: Compared with normal group ,mold (43.40% ± 2.67% vs 7.45% ± 1.26%, 38.60% ± 3.53% vs 13.70% ± 2.45%, P <0.01) in the phosphorylated p-ATF2 and PBL of the model group, (P <0.01). The positive rates of p-ATF2 and Bcl-2 in SB203580 group were significantly lower than those in the model group (27.70% ± 3.02% vs 58.70% ± 3.09%, 20.30% % ± 2.87%, P <0.01). The apoptosis rate of PBL in model group was significantly higher than that in model group (46.60% ± 4.14%, P <0.01) (2.42 ± 0.30 vs 0.28 ± 0.29, 5.42 ± 0.30 vs 0.30 ± 0.48, 3.29 ± 0.26 vs 0.05 ± 0.20, P <0.01). Compared with model group, SB203580 decreased significantly (1.24 ± 0.17, 3.30 ± 0.22, 1.10 ± 0.74, P <0.01) .Conclusion: P38MAPK inhibitor SB203580 can reduce the damage of intestinal inflammation in UC rats by decreasing the activity of p-ATF2 and the expression of Bcl-2 and promoting the apoptosis of PBL, which has the protective effect on UC.