木犀草素通过抑制PTEN PI3K-AKT信号通路以及对免疫功能的调节作用介导对肺癌模型大鼠的干预研究  

Effects of Luteolin on the Expression of PTEN PI3K-AKT Signaling Pathway and Immune Function in Lung Cancer Model Rats

作　　者：周亮[1] 乔印玲 王莉[1] 朱蕾 张建勇[1] 

机构地区：[1]遵义医学院附属医院呼吸二科 [2]贵州省航天医院妇科,遵义563000

出　　处：《天然产物研究与开发》2017年第12期2128-2133,2140,共7页Natural Product Research and Development

基　　金：贵州省科技计划(黔科合LH字[2016]7473号)

摘　　要：探讨木犀草素对肺癌模型大鼠的干预作用及其对PTEN-PI3K-AKT信号通路的抑制作用和对免疫功能的影响。采用灌注致癌碘油液制备大鼠肺癌模型,分别给予木犀草素高、中、低剂量和环磷酰胺治疗16周后进行大鼠的一般情况、肺组织病理形态学和肺脏指数、脾脏指数变化的评价。酶联免疫吸附法检测各组大鼠EGF、TGF-β、VEGF的表达。流式细胞术检测各组大鼠T淋巴细胞群(CD3^+、CD4^+、CD8^+、CD4^+/CD8^+)水平。实时荧光定量PCR法检测各组大鼠AKT-1、CyclinD1、NF-κB mRNA的表达。Western blot法检测各组大鼠PTEN、p-PI3K、p-AKT蛋白的表达。结果表明木犀草素可显著改善肺癌大鼠肺组织病理情况,提高脾指数,降低肺指数,提高血CD3^+、CD4^+、CD4^+/CD8^+水平,降低CD8^+水平,显著降低肺组织中EGF、TGF-β、VEGF的表达及AKT-1、CyclinD1、NF-κB mRNA的表达水平,提高肺组织中PTEN蛋白的表达,降低P-PI3K、p-AKT蛋白表达水平。木犀草素可显著抑制肺癌的增殖和转移,其机制可能与促进免疫器官的发育和分化,促进T淋巴细胞亚群的功能,提高机体免疫功能和下调PI3K/AKT信号通路的活性来发挥作用的。To investigate the effect of luteolin on PTEN-PI3K-AKT signal pathway and immune function in lung cancer model rats. The rats were given disposable infusion of carcinogenic iodized oil via left lobe bronchus to induce lung canc- er model. The rats were treated with high, medium and low dose of luteolin and cyclophosphamide respectively for 16 weeks. The general condition, histopathology and lung index, spleen index were evaluated. The expression of EGF, TGF-fl and VEGF was detected by enzyme-linked immunosorbent assay （ELISA）. The CD3 ＋ , CD4 ＋ ,CD8 ~ , CIM ＋/CD8 ＋ in T lymphocytes of rats were detected by flow cytometry. The expression of AKT-1, CyclinD1 and NF-KB mRNA in each group were detected by Real-time fluorescent quantitative PCR. The expression of PTEN, p-PI3K and p-AKT protein was detected by Western blot. The results showed that luteolin can significantly improve the pathology of lung tissue, decrease the lung index and increase spleen index. Luteolin cannot only reduce the levels of EGF,TGF-fl, VEGF and AKT-1, Cy- elinD1, NF-KB mRNA and P-PI3 K and p-AKT protein in lung tissue and the expression of CD8 ~ levels in blood, but al- so increase the expression of CD3 ＋ , CIM ~ , CIM ＋/CD8 ＋ levels in blood and PTEN protein in lung tissue. Luteolin can significantly improve the immune function and downregulate the activity of PI3K/AKT signaling pathway in the Lung Cancer Model Rats.

关 键 词：木犀草素 肺癌 肺指数 脾指数 PTEN-PI3K-AKT 

分 类 号：R73[医药卫生—肿瘤] X70[医药卫生—临床医学]