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目的探讨磷脂酰肌醇3激酶(PI3K)/Akt 信号传导通路在溃疡性结肠炎(UC)发病中的作用并为沃特曼宁(wortmannin)作为 UC 治疗新药物提供实验依据。方法收集 UC 患者30例,15例结肠癌旁正常组织作为对照,采用免疫组化法检测 UC 肠黏膜组织中磷酸化 Akt(p-Akt)的表达情况;体外组织培养观察 PI3 K/Akt 信号传导通路抑制剂 wortmannin 对 UC 肠黏膜活检组织肿瘤坏死因子(TNF)-α表达的影响。结果①UC 肠黏膜组织中 p-Akt 的表达明显高于正常对照组(A 值分别为73.6±5.2、18.0±2.6,阳染面积分别为720±58、133±29,均 P<0.05)。②与未用 wortmannin处理的 UC 对照组比较,wortmannin 处理后 UC 肠黏膜组织分泌 TNF-α的水平明显较低(分别为296±39、138±11、26±5,均 P<0.05)。③用 wortmannin 处理后 UC 患者肠黏膜组织中 p-Akt 的表达低于未用 wortmannin 处理的 UC 对照组(A 值分别为:72.3±6.2、35.3±5.6、18.0±2.2,阳染面积分别为716±94、351±50、129±30,均 P<0.05)。结论①PI3K/Akt 信号转导通路参与了促炎性细胞因子 TNF-α的调控与释放,可能在 UC 的发生发展中起着重要作用。②PI3K 的抑制剂 wortmannin 能阻断 PI3K/Akt 信号转导通路,进而减少细胞因子的释放。wortmannin 有可能成为治疗 UC 的新药物。
Objective To investigate the role of phosphatidylinositol 3 kinase (PI3K) / Akt signaling pathway in the pathogenesis of ulcerative colitis (UC) and to provide experimental evidence for wortmannin as a new drug for the treatment of UC. Methods 30 cases of UC patients and 15 cases of adjacent normal colon tissues were collected as control. The expression of phosphorylated Akt (p-Akt) in UC intestinal mucosa was detected by immunohistochemistry. PI3K / Akt signaling was observed in vitro Effect of wortmannin, a pathway inhibitor, on the expression of tumor necrosis factor (TNF) - α in the intestinal mucosa of UC patients. Results ① The expression of p-Akt in UC intestinal mucosa was significantly higher than that in the normal control group (A values were 73.6 ± 5.2 and 18.0 ± 2.6, respectively, and the area of positive staining was 720 ± 58 and 133 ± 29, P <0.05 respectively). ② The levels of TNF-α secreted by wortmannin in UC intestinal mucosa were significantly lower than those in UC without wortmannin treatment (296 ± 39,138 ± 11,26 ± 5, P <0.05, respectively). (3) The expression of p-Akt in UC patients with wortmannin treatment was lower than that in UC patients without wortmannin treatment (A values were 72.3 ± 6.2,35.3 ± 5.6,18.0 ± 2.2, respectively, and the areas with positive staining were 716 ± 94,351 ± 50,129 ± 30, all P <0.05). Conclusion PI3K / Akt signaling pathway is involved in the regulation and release of proinflammatory cytokine TNF-α, which may play an important role in the development and progression of UC. PI3K inhibitor wortmannin can block the PI3K / Akt signal transduction pathway, thereby reducing the release of cytokines. wortmannin may become a new drug for the treatment of UC.