益肾通淋方对良性前列腺增生大鼠PI3K/Akt/mTOR信号通路的影响
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摘要
目的观察益肾通淋方对良性前列腺增生(BPH)大鼠前列腺PI3K/Akt/mTOR信号通路的影响,探讨其作用机制。方法采用去势联合丙酸睾酮注射方法建立BPH模型,对照组行假手术。将60只SD大鼠随机分为对照组、模型组、阳性药组和益肾通淋方高、低剂量组,每组12只。于去势第8日开始灌胃给药,每日1次,连续28d。末次给药后1h,大鼠麻醉取前列腺,计算前列腺指数,HE染色观察前列腺组织病理形态,Western blot和RT-PCR分别检测前列腺PI3K/Akt/mTOR信号通路蛋白和m RNA的表达。结果与对照组比较,模型组大鼠前列腺明显增生,PI3K、Akt和m TOR磷酸化蛋白及m RNA表达均显著升高,PI3K/Akt/mTOR信号通路激活;益肾通淋方干预后,模型大鼠前列腺指数下降,腺体变少,腺腔扩张,前列腺增生明显缓解,同时PI3K、Akt和m TOR蛋白磷酸化水平降低,m RNA表达显著下调。结论益肾通淋方能有效改善BPH大鼠前列腺增生,其作用机制可能与抑制PI3K/Akt/mTOR信号通路有关。
Objective To investigate the effects of Yishen Tonglin Prescription on prostate PI3 K/Akt/mTOR signaling pathway in benign prostatic hyperplasia(BPH) rats; To discuss its mechanism of action. Methods The BPH model was established by the method of castration combined with testosterone propionate injection. The control group received sham-operation. Totally sixty SD rats were randomly divided into control group, model group, positive medicine group, and Yishen Tonglin Prescription high-and low-dosage groups, with 12 rats in each group. Gavage was started on the 8 th day after castration, once a day for 28 days. One hour after the last administration, the rats were anesthetized, and the prostate tissue was taken to calculate the prostate index. The pathological changes of prostate tissue were observed by HE staining. The expression levels of protein and m RNA in prostate PI3 K/Akt/mTOR pathway were detected by Western blot and RT-PCR respectively. Results Compared with the control group, the prostatic hyperplasia was evident in the model group, the phosphorylation level and mRNA expression of PI3 K, Akt and mTOR significantly increased, and the PI3 K/Akt/mTOR pathway was activated. After the intervention of Yishen Tonglin Prescription, the prostate index of the model rats decreased, the glands become fewer, the glandular cavity dilated, the prostate hyperplasia was relieved, the phosphorylation levels of PI3 K, Akt and mTOR decreased, and the m RNA expression was significantly down-regulated. Conclusion Yishen Tonglin Prescription can effectively improve prostatic hyperplasia in BPH rats, and its mechanism may be related to inhibition of PI3 K/Akt/mTOR signaling pathway.
Objective To investigate the effects of Yishen Tonglin Prescription on prostate PI3 K/Akt/mTOR signaling pathway in benign prostatic hyperplasia(BPH) rats; To discuss its mechanism of action. Methods The BPH model was established by the method of castration combined with testosterone propionate injection. The control group received sham-operation. Totally sixty SD rats were randomly divided into control group, model group, positive medicine group, and Yishen Tonglin Prescription high-and low-dosage groups, with 12 rats in each group. Gavage was started on the 8 th day after castration, once a day for 28 days. One hour after the last administration, the rats were anesthetized, and the prostate tissue was taken to calculate the prostate index. The pathological changes of prostate tissue were observed by HE staining. The expression levels of protein and m RNA in prostate PI3 K/Akt/mTOR pathway were detected by Western blot and RT-PCR respectively. Results Compared with the control group, the prostatic hyperplasia was evident in the model group, the phosphorylation level and mRNA expression of PI3 K, Akt and mTOR significantly increased, and the PI3 K/Akt/mTOR pathway was activated. After the intervention of Yishen Tonglin Prescription, the prostate index of the model rats decreased, the glands become fewer, the glandular cavity dilated, the prostate hyperplasia was relieved, the phosphorylation levels of PI3 K, Akt and mTOR decreased, and the m RNA expression was significantly down-regulated. Conclusion Yishen Tonglin Prescription can effectively improve prostatic hyperplasia in BPH rats, and its mechanism may be related to inhibition of PI3 K/Akt/mTOR signaling pathway.
引文
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[11]贾艳菊,季晖.PI3K/Akt/mTOR信号传导通路与前列腺癌关系的研究进展[J].药学与临床研究,2015,23(2):160-163.
[2]HAN Z,ZHANG L,ZHU R,et al.Relationship of oestrogen receptor alpha gene polymorphisms with risk for benign prostatic hyperplasia and prostate cancer in Chinese men[J].Medicine(Baltimore),2017,96(13):e6473.
[3]IQBAL J,AL-RASHED J,KEHINDE E O.Detection of Trichomonas vaginalis in prostate tissue and serostatus in patients with asymptomatic benign prostatic hyperplasia[J].BMC Infect Dis,2016,16(1):506-511.
[4]PARK H K,KIM S K,LEE S W,et al.A herbal formula,comprising Panax ginseng and bee pollen,inhibits development of testosterone induced benign prostatic hyperplasia in male Wistar rats[J].Saudi J Biol Sci,2017,24(7):1555-1561.
[5]袁轶峰,傅显文,朱文雄,等.益气活血消癥方对良性前列腺增生大鼠细胞凋亡的影响[J].中国中医药信息杂志,2018,25(9):52-55.
[6]ISHOLA I O,YEMITAN K O,AFOLAYAN O O,et al.Potential of moringa oleifera in the treatment of benign prostate hyperplasia:role of antioxidant defence systems[J].Med Princ Pract,2018,27(1):15-22.
[7]WU D D,GAO Y R,LI T,et al.PEST-containing nuclear protein mediates the proliferation,migration,and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways[J].BMC Cancer,2018,18(1):499-513.
[8]WU X,YU J,YAN J,et al.PI3K/AKT/mTOR pathway inhibitors inhibit the growth of melanoma cells with mTOR H2189Y mutations in vitro[J].Cancer Biol Ther,2018,19(7):584-589.
[9]XIA P,XU X Y.PI3K/Akt/mTOR signaling pathway in cancer stem cells:from basic research to clinical application[J].Am J Cancer Res,2015,5(5):1602-1609.
[10]乔铁,梁可,马进,等.黄芪皂苷对化疗贫血小鼠PI3K/Akt/mTOR信号通路相关基因mRNA表达的影响[J].中国中药杂志,2016,41(20):3828-3832.
[11]贾艳菊,季晖.PI3K/Akt/mTOR信号传导通路与前列腺癌关系的研究进展[J].药学与临床研究,2015,23(2):160-163.