蠲痛饮对子宫内膜异位症大鼠PI3K/Akt/mTOR信号通路蛋白的影响  

Effect of Juantong Decoction on PI3K/Akt/mTOR Signaling Pathway Proteins in Rats with Endometriosis

作　　者：张亚萍[1,2] 李卫红[1] 李婧[3] 李卫民 韦玉竹[1] ZHANG Ya-ping;LI Wei-hong;LI Jing;LI Wei-min;WEI Yu-zhu(Guangxi University of Chinese Medicine,Narming 530200,China;Hubei University of Chinese Medicine,Wuhan 430065,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]广西中医药大学,南宁530200 [2]湖北中医药大学,武汉430065 [3]北京中医药大学,北京100029

出　　处：《中国实验方剂学杂志》2019年第16期24-30,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：广西自然科学基金面上项目(2015GXNSFAA139112);广西中医药大学校级重点课题项目(ZD2012001)

摘　　要：目的:探讨蠲痛饮对子宫内膜异位症(EMS)大鼠磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素靶分子(mTOR)信号通路蛋白的影响。方法:采用自体子宫内膜移植法建立EMS大鼠模型,随机将48只大鼠分为正常组、模型组、蠲痛饮低、中、高剂量组、通路阻滞剂组(LY294002) 6组,分别给予蠲痛饮高、中、低剂量(42. 9,14. 3,4. 8 g·kg^-1)灌胃,通路阻滞剂组予PI3K通路阻滞剂LY294002(0. 04 g·kg^-1)腹腔注射,正常组及模型组每天按照10 mL·kg^-1给予生理盐水灌胃,各组持续用药28 d。应用透射电镜观察大鼠异位内膜组织超微结构,免疫组化法检测异位内膜组织PI3K,Akt,mTOR蛋白表达,实时荧光定量聚合酶链式反应(Real-time PCR)检测核糖体蛋白S6激酶(p70S6K) mRNA相对含量。结果:与正常组比较,模型组异位内膜PI3K,Akt,mTOR蛋白和p70S6K mRNA的表达都明显升高(P<0.05);与模型组比较,蠲痛饮中、高剂量、通路阻滞剂组干预后PI3K,Akt,mTOR蛋白和p70S6K mRNA的表达明显降低(P<0.05)。透射电镜下可见蠲痛饮低、中、高剂量组和通路阻滞剂组均能促进腺上皮细胞萎缩或欠整齐,微绒毛减少或消失,胞核固缩,胞内线粒体肿胀或减少,间质细胞凋亡。结论:PI3K/Akt/mTOR信号通路参与子宫内膜异位症发生;蠲痛饮可能通过下调PI3K/Akt/mTOR通路蛋白的表达及p70S6K mRNA表达,从而抑制上皮间质细胞活性,促进细胞凋亡,治疗子宫内膜异位症。Objective: To discuss the effect of Juantong decoction on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin( PI3K/Akt/mTOR) signaling pathway proteins in rats with endometriosis( EMS). Method: The EMS Rat model was established by autologous endometrial transplantation.And 48 rats were randomly divided into 6 group,namely the sham operation group,the model group,the low-dose Juantong decoction group,the middle-dose Juantong decoction group,high-dose Juantong decoction group,and the PI3K pathway blocker group( LY294002). Then,the high-dose Juantong decoction group,the middle-dose Juantong decoction group and the low-dose Juantong decoction group were given different doses( 42. 9,14. 3,4. 8 g·kg^-1). The pathway blocker group( LY294002) was given LY294002( 0. 04 g·kg^-1) through peritoneal injection weekly. The sham operation group and the model group were given saline irrigation( 10 mL·kg^-1). The administration lasted for 28 days. At last,the ectopic endometrial tissues in rats were observed by transmission electron microscope,the proteins of PI3K,Akt and mTOR in the tissue were detected by immunohistochemical method,and the p70 ribosomal S6 kinase( p70 S6 K) mRNA expression of ectopic endometrial tissue was tested by Real-time fluorescence quantitative polymerase chain reaction( Real-time PCR) method. Result: Compared with the normal group,the protein expressions of PI3K,Akt and mTOR and the mRNA expression of p70 S6 K of ectopic endometrium in the model group increased significantly( P < 0. 05). And compared with the model group,the protein expressions of PI3K,Akt and mTOR and the mRNA expression of p70S6K decreased significantly after the intervention with middle and high doses of Juantong decoction and Western medicine Group( P < 0. 05). Under the lens,the glandular epithelial cells in middle and high-dose Juantong decoction and western medicine groups were atrophy or untidy,the microvilli decreased or disappeared,the cell nuclei were shrunk,the mitochondria were visible,and there wer

关 键 词：蠲痛饮 子宫内膜异位症 磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素靶分子(mTOR)信号通路 当归芍药散 芍药甘草汤 

分 类 号：R2-0[医药卫生—中医学] R22