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目的探讨溃疡性结肠炎(UC)患者肠黏膜组织中磷酸化 p38丝裂原活化蛋白激酶(p38 MAPK)的表达及 p38 MAPK 抑制剂 SB203580对活动性 UC 患者肠黏膜组织 TNFα表达的影响。方法 30例活动性 UC 患者被纳入本研究,以15例结肠癌患者的癌旁正常组织作为对照。免疫组化法检测 UC 患者肠黏膜活检组织中磷酸化 p38 MAPK 的表达。体外组织培养条件下观察 SB203580对UC 患者肠黏膜组织 TNFα表达的影响,ELISA 法检测培养上清液中 TNFα含量。结果(1)UC 患者肠黏膜磷酸化 p38 MAPK 的表达明显高于正常肠黏膜,A 值分别为549.22±32.54、143.52±11.89,阳染面积分别为[(1680.61±115.30)×10~(-5)、(351.68±12.73)×10~(-5)]μm~2,P 值均<0.01。(2)与未用 SB203580处理的 UC 组比较,处理后 UC 肠黏膜组织分泌 TNFα的水平明显较低,分别为(549.96±107.63、72.07+20.30)ng/L(P<0.01)。(3)与未用 SB203580处理的 UC 组比较,处理后 UC 肠黏膜组织 p38 MAPK 下游分子活化转录因子-2(ATF_2)的活性表达明显减少,A 值分别为688.32±47.37、265.82±40.25,阳染面积分别为[(2489.02±193.63)×10~(-5)、(1213.76±204.77)×10~(-5)]μm~2,P 值均<0.01,但对磷酸化 p38 MAPK 的表达无影响,A 值分别为480.34±38.87、465.64±38.69,阳染面积分别为[(1536.68±182.16)×10~(-5)、(1486.26±165.49)×10~(-5)]μm~,P 值均>0.05。结论 p38 MAPK 信号传导通路在 UC 的发病中起着重要作用,阻断该通路可减少炎性细胞因子的释放。提示 p38 MAPK 信号传导通路可以为 UC 的治疗提供一个新的靶标,SB203580有可能成为 UC 治疗的新药物。
Objective To investigate the expression of phospho-p38 mitogen-activated protein kinase (p38 MAPK) in intestinal mucosa of patients with ulcerative colitis (UC) and the effect of p38 MAPK inhibitor SB203580 on the expression of TNFα in intestinal mucosa of patients with active UC. Methods Thirty active UC patients were enrolled in this study. The normal tissue adjacent to the tumor in 15 patients with colon cancer was used as a control. Immunohistochemistry was used to detect the expression of phospho-p38 MAPK in intestinal mucosa biopsy of UC patients. The effect of SB203580 on the expression of TNFα in intestinal mucosa of UC patients was observed under in vitro culture conditions. The content of TNFα in culture supernatant was detected by ELISA. Results (1) The expression of phosphorylated p38 MAPK in intestinal mucosa of UC patients was significantly higher than that of normal intestinal mucosa (A value 549.22 ± 32.54,143.52 ± 11.89, respectively), and the area of positive staining were [(1680.61 ± 115.30) × 10 -5 ), (351.68 ± 12.73) × 10 ~ (-5)] μm ~ 2, P <0.01. (2) Compared with UC group without SB203580 treatment, the levels of TNFα secreted by UC intestinal mucosa were significantly lower (549.96 ± 107.63, 72.07 + 20.30) ng / L (P <0.01). (3) Compared with UC group without SB203580 treatment, the expression of ATF2 in p38 MAPK of UC intestinal mucosa significantly decreased after treatment, with the A values of 688.32 ± 47.37 and 265.82 ± 40.25, respectively (2489.02 ± 193.63) × 10 ~ (-5), (1213.76 ± 204.77) × 10 ~ (-5)] μm ~ 2, P values were all <0.01, but the expression of phosphorylated p38 MAPK was , The values of A were 480.34 ± 38.87 and 465.64 ± 38.69, respectively, and the areas of the positive staining were [(1536.68 ± 182.16) × 10 -5 and (1486.26 ± 165.49) × 10 -5] μm, P Value> 0.05. Conclusion The p38 MAPK signal transduction pathway plays an important role in the pathogenesis of UC. Blocking this pathway can reduce the release of inflammatory cytokines. It is suggested that p38 MAPK signal transduction pathway can provide a new target for the treatment of UC, SB203580 may become a new drug for UC treatment.