磷脂酰肌醇3激酶信号转导通路与Barrett食管发生的实验研究

Experimental study on phosphatidylinositol 3 kinase signal transduction pathway in Barrett esophagusgenesis

目的探讨磷脂酰肌醇3激酶（P13K）／蛋白激酶B（Akt）／哺乳动物雷帕霉素靶蛋白（mTOR）信号转导通路与Barrett食管发生的关系。方法将140只大鼠分为假手术组10只、铁剂组10只、食管十二指肠端侧吻合组30只、食管十二指肠端侧吻合加铁剂组30只、食管胃十二指肠侧侧吻合组30只、食管胃十二指肠侧侧吻合加铁剂组30只。最后共获得10份正常食管组织、62份反流性食管炎组织、34份Barrett食管组织，应用免疫组织化学方法检测以上3种组织中表皮生长因子受体（EGFR）、Akt、磷酸化Akt和磷酸化mTOR蛋白的表达水平。采用单因素方差分析、SNK两两比较和非参数相关性分析进行统计学处理。结果Barrett食管组织中EGFR、Akt、磷酸化Akt、磷酸化mTOR蛋白的表达水平高于反流性食管炎和正常的食管组织（EGFR为0．1799±0．0367比0．0438±0．0025和0．0277±0．0069，q=6．79、4．13；Akt为0．1874±0．0250比0．0986±0．0093和0．0383±0．0048，q=6．51、3．56；磷酸化Akt为0．1418±0．0130比0．0592±0．0027和0．0281±0．0017，q=7．68、3．99；磷酸化mTOR为0．1591±0．0275比0．0674±0．0059和0．0112±0．0017，q=5．62、4．11，P均〈0．05）。反流性食管炎食管组织中EGFR、Akt、磷酸化Akt、磷酸化mTOR蛋白的表达水平高于正常食管组织（q=4．67、4．29、4．27、4．03，P均〈O．05）。结论反流性食管炎、Barrett食管组织中P13K／Akt／mTOR信号转导通路被激活，为临床多靶点治疗疾病提供了一定的理论依据。

Objective To explore the relationship between phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammals target protein rapamycin （mTOR） signal transduction pathway and Barrett esophagus genesis. Methods A total of 140 rats were divided into sham-operated group （n = 10）, iron group （n=10）, esophageal duodenal side anastomosis group （n = 30）, esophageal duodenal side anastomosis plus iron group （n= 30）, esophageal gastric duodenal side anastomosis group （n= 30） and esophageal gastric duodenal anastomosis plus iron group （n=30）. In the end, 10 normal esophagus tissue specimens, 62 reflux esophagitis tissue specimens and 34 Barrett＇s esophagus tissue specimens were obtained. The expression levels of epidermal growth factor receptor （EGFR）, Akt, phospho-Akt（p-Akt）, phospho-mTOR（p-mTOR） protein were detected byimmunohistochemistry. Single factor analysis of variance, SNK between two groups and nonparametric correlation analysis were performed for statistical analysis. Results The protein expression levels of EGFR, Akt, p-Akt, p-mTOR in Barrett＇s esophagus tissues were higher than those in reflux esophagitis tissues and normal esophagus tissues （EGFR 0. 1799±0. 0367 vs 0. 0438±0. 0025 and 0. 0277±0. 0069, q=6.79, 4.13; Akt 0. 1874±0. 0250 vs 0. 09864-0. 0093 and 0. 0383± 0. 0048, q=6.51, 3.56; p-Akt 0. 1418±0. 0130 vs 0. 0592-t-0. 0027 and 0. 0281±0. 0017, q=7.68, 3.99; p-mTOR 0. 1591±0. 0275 vs 0. 0674520. 0059 and 0. 0112±0. 0017,q=5.62, 4.11; all P〈 0.05）. The protein expression levels of EGFR, Akt, p-Akt, and p-mTORin reflux esophagitis tissues were higher than those in normal esophagus tissues（q= 4.67, 4.29, 4. 27, 4.03; all P〈0.05）. Conelusion PI3K/Akt/mTOR signal transduction pathway were activated in reflux esophagitis and Barrett＇s esophagus, which provided theoretical basis for clinical multi-target treatment for diseases.