盐酸坦索罗辛对前列腺增生大鼠P13K/Akt信号通路的影响  

Effect of tamsulosin hydrochloride on the P13K/Akt signaling pathway in benign prostatic hyperplasia rats

作　　者：张杜平 崔振鹏 刘鹤 毛文博 刘鸿燕 刘山 廖东云 罗林 Zhang Duping;Cui Zhenpeng;Liu He;Mao Wenbo;Liu Hongyan;Liu Shan;Liao Dongyun;Luo Lin(Department of Urology,521 Hospital of Weaponry Industry,Xi’an 710065,China)

机构地区：[1]兵器工业五二一医院,西安710065

出　　处：《广西医科大学学报》2020年第5期850-855,共6页Journal of Guangxi Medical University

摘　　要：目的:探讨盐酸坦索罗辛对前列腺增生(BPH)大鼠P13K/Akt信号通路的影响。方法:将健康的雄性SD大鼠60只随机分为健康对照组、空白模型组和盐酸坦索罗辛高、中、低剂量组,每组12只。除健康对照组外,其余各组大鼠均采用去势术联合丙酸睾酮注射建立良性BPH模型。建模成功后,盐酸坦索罗辛高、中、低剂量组分别灌胃1 mL剂量为0.1 mg/mL、0.2 mg/mL和0.4 mg/mL的盐酸坦索罗辛配制溶液,健康对照组和空白模型组灌胃等体积的蒸馏水。治疗28 d后计算大鼠前列腺指数,苏木精-伊红(HE)染色观察前列腺组织病理改变,免疫组化超敏感SP法检测Ki-67蛋白的表达情况,利用Ki-67蛋白表达计算出细胞增殖指数。Western blotting检测前列腺PI3K/Akt信号通路相关蛋白p-PI3K、p-Akt和p-mTOR蛋白相对表达量。实时荧光定量聚合酶链反应(qPCR)检测PI3K、Akt和mTOR蛋白mRNA相对表达量。结果:HE染色结果显示,健康对照组的大鼠前列腺结构完整,腺体和腺腔大小正常,腺上皮细胞排列整齐;建模各组大鼠前列腺腺体增生明显,腺腔缩小,腺上皮细胞皱褶增多,盐酸坦索罗辛高、中、低剂量组大鼠的前列腺腺体增生较空白模型组大鼠明显减少,盐酸坦索罗辛中剂量组改善程度明显优于盐酸坦索罗辛低剂量组、高剂量组。各组大鼠前列腺指数、P13K/Akt信号通路相关蛋白表达和细胞增殖指数比较,均具有显著差异(均P<0.01),盐酸坦索罗辛高、中、低剂量组比健康对照组高(P<0.05),且比空白模型组低(P<0.05),盐酸坦索罗辛中剂量组表现更明显。p-PI3K、p-Akt和p-mTOR蛋白相对表达量与前列腺指数呈正相关关系(P<0.05)。结论:盐酸坦索罗辛能抑制前列腺细胞增殖,有效改善BPH模型大鼠前列腺组织增生,其可能作用机制与抑制PI3K/Akt信号通路表达相关。Objective:To explore the effect of tamsulosin hydrochloride on the P13 K/Akt signaling pathway in benign prostatic hyperplasia(BPH)rats.Methods:Sixty healthy male SD rats were randomly divided into healthy control group,blank model group and tamsulosin hydrochloride high,medium and low dose groups,with12 rats in each group.Except for the healthy control group,the other groups of rats were usedcastrationcombined with testosterone propionate injectionto establish BPH rat models.After successful modeling,the tamsulosin hydrochloride high,medium and low dose groups were given 1 mL of 0.4 mg/mL,0.2 mg/mL and 0.1 mg/mL tamsulosin hydrochloride solutions by gavage,respectively,and the same volume of distilled water was given to the healthy control and blank model groups.After 28 days of treatment,the prostate index of rats was calculated.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of the prostate tissue.The expression of Ki-67 protein was detected by super sensitive streptavidin-peroxidase(SP)immunohistochemistry,and cellular proliferationindexwas calculated base onKi-67 protein expression.Western blotting was used to detect the relative expression of p-PI3 K,p-Akt and p-mTOR proteins that related with the PI3 K/Akt signaling pathway in prostate cells.Real-time fluorescence quantitative polymerase chain reaction(qPCR)was used to detect the relative expression of PI3 K,Akt and mTOR mRNA.Results:The results of HE staining showed that the structure of the prostate in the healthy control group was intact,the gland and cavity were normal in size,and the glandular epithelial cells were arranged neatly;the prostatic gland hyperplasia in the model rats of each group was obvious,the cavity was reduced,and the folds ofglandular epithelial cellwasincreased;the prostate gland hyperplasia in the tamsulosin hydrochloride groups were significantly reduced compared with the blank model group,and this phenomenonwas more obvious in the tamsulosin hydrochloride medium dose group than that in the tamsulosin h

关 键 词：盐酸坦索罗辛 P13K/AKT信号通路 前列腺增生 

分 类 号：R69[医药卫生—泌尿科学]