基于PI3K/Akt信号通路研究升降通癃方中空栓对前列腺增生大鼠的影响  

Effect of Shengjiang Tonglong Prescription Hollow Suppository on Rats with Prostatic Hyperplasia Based on PI3K/Akt Signaling Pathway

作　　者：胡黄金 雷利娟 赵鹏 郑靓怡 杨妮 孟春慧 孟婼娅 张恒[3] HU Huangjin;LEI Lijuan;ZHAO Peng;ZHENG Jingyi;YANG Ni;MENG Chunhui;MENG Ruoya;ZHANG Heng(Shanxi University of Chinese Medicine,Jinzhong 030619,China;Huangshi Hospital of Traditional Chinese Medicine(TCM),Huangshi 435000,China;Shanxi Provincial Institute of TCM,Taiyuan 030012,China)

机构地区：[1]山西中医药大学,山西晋中030619 [2]黄石市中医医院,湖北黄石435000 [3]山西省中医药研究院,太原030012

出　　处：《中国实验方剂学杂志》2022年第19期89-96,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：山西省重点研发计划项目(201903D321232)。

摘　　要：目的:通过观察升降通癃方中空栓对前列腺增生大鼠前列腺中双氢睾酮(DHT)的水平、及前列腺中磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路相关蛋白的影响,探究升降通癃方中空栓治疗前列腺增生大鼠的机制。方法:从60只SD雄性大鼠中随机选取10只为假手术组,其余大鼠经去势后连续4周皮下注射丙酸睾丸酮造前列腺增生大鼠模型,采用随机数字表法随机分为模型组、非那雄胺(0.45 mg·kg^(-1))组、升降通癃方中空栓高、中、低剂量(3.98、1.99、0.99 g·kg^(-1))组,每组10只。去势7 d后,假手术组及模型组选用空白中空栓、非那雄胺组及升降通癃方中空栓组选用相应中空栓,连续肛塞直肠给药28 d。杀检大鼠,分离并称量前列腺组织,观察药物对各组大鼠前列腺指数的影响,苏木素-伊红(HE)染色前列腺组织进行病理观察,酶联免疫吸附测定法(ELISA)检测DHT的水平,并采用蛋白免疫印迹法检测前列腺组织PI3K/Akt信号通路蛋白及B细胞淋巴瘤-2(Bcl-2)、胱天蛋白酶-3(Caspase-3)、Bcl-2相关X蛋白(Bax)、αB-晶状体蛋白(CRYAB)蛋白表达水平。结果:与假手术组比较,模型组大鼠前列腺指数显著升高,光镜下模型组大鼠前列腺明显增生,DHT水平明显升高,CRYAB、Bcl-2、PI3K及Akt蛋白表达水平上升,Caspase-3及Bax蛋白表达水平下降(P<0.05,P<0.01)。与模型组比较,升降通癃方中空栓高剂量组大鼠前列腺指数下降(P<0.05),升降通癃方中空栓各剂量组大鼠前列腺中DHT水平、CRYAB、Bcl-2、PI3K及Akt蛋白表达水平下降,Caspase-3及Bax蛋白表达水平上升(P<0.05,P<0.01)。结论:升降通癃方中空栓可通过降低CRYAB蛋白表达,负性调控PI3K/Akt信号通路,下调DHT水平,Bcl-2、PI3K及Akt蛋白表达水平,上调Caspase-3及Bax蛋白表达水平,抑制细胞增殖和促进细胞凋亡,从而发挥对BPH的治疗作用;高剂量升降通癃方中空栓改善大鼠前列腺增生效果显著。Objective:To investigate the effect of Shengjiang Tonglong prescription hollow suppository on rats with prostate hyperplasia,and the effect of the proteins related to phosphoinositide 3-kinase/protein kinase B(PI3K/Akt)signaling pathway in the prostate,thus exploring the mechanism of Shengjiang Tonglong prescription hollow suppository in the treatment of rats with prostate hyperplasia.Method:Ten SD male rats were randomly selected from 60 SD male rats to form a sham operation control group,and the rest rats were subcutaneously injected with testosterone propionate for 4 consecutive weeks after castration to induce the rat model of prostatic hyperplasia.According to the random number table method,the 50 rats were randomly divided into a model group,a finasteride group(0.45 mg·kg^(−1)),and three high,middle,and low-dose Shengjiang Tonglong prescription hollow suppository groups(3.98,1.99,0.99 g·kg^(−1)),with ten rats in each group.After castration for 7 d,the sham operation control group and the model group used the blank hollow suppositories,and the finasteride group and the Shengjiang Tonglong prescription hollow suppository groups used the corresponding hollow suppositories.The drugs were given to the rats by anal plugs continuously for 28 d.The rats were then killed,and the prostate tissues were separated and weighed to observe the effects of drugs on the prostate index of rats in each group.The hematoxylin-eosin(HE)staining was used for the pathological observation of the prostate tissues.The level of dihydrotestosterone(DHT)was detected by enzymelinked immunosorbent assay(ELISA).Western blot was used to detect the expression levels of PI3K/Akt signaling pathway protein,B-cell lymphoma-2(Bcl-2),cysteine aspartate-specific protease-3(Caspase-3),Bcl-2-associated X protein(Bax),andαB-crystallin(CRYAB)protein in the prostate tissues.Result:As compared with the sham operation control group,the protein expression levels of prostate index,DHT level,CRYAB,Bcl-2,PI3K,and Akt in the model group were increased,and

关 键 词：升降通癃方中空栓 前列腺增生 αB-晶状体蛋白(CRYAB) 磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路 

分 类 号：R285.5[医药卫生—中药学] R966[医药卫生—中医学] R697R-33