α1a肾上腺素受体拮抗剂西洛多辛对大鼠良性前列腺增生的影响被引量：2

Effect of silodosin, an alphal a-adrenoceptor antagonist, on benign prostatic hyperplasia in rat

导出

摘要目的探讨选择性α1a肾上腺素受体拮抗剂西洛多辛对睾酮引起大鼠良性前列腺增生（BPH）的影响及机制研究。方法大鼠随机分成三组：对照组、睾酮诱导BPH组和西洛多辛＋BPH组。对照组不做任何处理，BPH组、西洛多辛组BPH模型由睾酮[20mg／（kg·d）]皮下连续注射4周诱导。西洛多辛组大鼠同时连续口服西洛多辛[100μg／（kg·d）]4周，4周后处死所有大鼠，检测各组大鼠血生化指标，前列腺体积、重量和病理变化，表皮生长因子受体（EGFR）和B细胞慢性淋巴细胞白血病／淋巴瘤2（BCL-2）蛋白表达。结果4周后，各组大鼠体重均增加，但差异无统计学意义（P〉0．05）。BPH组血糖水平低于对照组，各组间谷草转氨酶和谷丙转氨酶水平差异均无统计学意义（P〉0．05）。与BPH组相比，西洛多辛治疗组前列腺体积和重量显著减小[前列腺体积：（0．93±0．14）cm^3 VS（1．75±0．15）cm^3，P〈0．01；前列腺重量：（0．97±O．06）gVS（1．30±0．05）g，P〈0．01]。西洛多辛降低前列腺组织中EGFR和BCL-2表达（P〈0．05）。结论西洛多辛可能通过减少EGFR和BCL-2的表达抑制BPH。 Objective To investigate the effect of silodosin, a selective alphalaadrenoceptor antagonist on a rat model of testosterone-induced benign prostatic hyperplasia （BPH） and its mechanisms. Methods The rats were divided into three groups： control, testosterone-induced BPH, and silodosin ＋ BPH groups. BPH was induced by subcutaneous injection of testosterone [20 mg/（ kg · d） ] for 4 weeks. Meanwhile silodosin ＋ BPH groups rats were administered silodosin 4 weeks [ 100 μg,/（ kg · d）]. After 4 weeks, all animals were sacrificed to examine the blood biochemical profiles, prostate volume, weight, histopathological changes, and epidermal growth factor receptor （EGFR） and B-cell chronic lymphocytic leu- kemia （CLL）/lymphoma 2 （BCL-2） protein expressions. Results Each group showed an increase compared to their initial body weight; however, differences in weight change between groups were not significant （ P 〉 0.05）. The BPH group displayed lower glucose levels than the control group. The serum levels of glutamic oxaloacetic transaminase （GOT） and glutamic pyruvic transaminase （Girl＇） were not significantly different among groups （ P 〉 0.05）. The group treated with silodosin showed significantly lesser prostate size and weight than the testosterone-induced BPH group [ volume：（0. 93 ± 0. 14）cm^3 vs （1.75 ± 0. 15 ） cm^3,P 〈0.01; weight：（0.97 ±0.06）g vs （1.30±0.05）g, P 〈0.01]. In addition, silodosin decreased the expressions of EGFR and BCL-2 in prostate tissues （ P 〈 0. 05）. Conclusions These results suggest that silodosin suppress the development of BPH by inhibiting the expressions of EGFR and BCL-2.

作者刘兵彭志锋

机构地区山西省大同煤矿集团有限责任公司二医院外科山西大同大学医学院生理教研室

出处《中国医师杂志》 CAS 2016年第2期199-202,207,共5页 Journal of Chinese Physician

基金山西省基础研究项目（2015021178）

关键词肾上腺素能β受体拮抗剂/药理学睾酮/副作用前列腺增生/病因学/药物疗法 Adrenergic beta-antagonists/PD Testosterone/AE Prostatic hyperplasia/ET/DT

分类号 R697.3 [医药卫生—泌尿科学]

引文网络
相关文献

参考文献15

1Griebling T. Prevalence and correlates of nocturia in communitydwelling older men: results from the korean longitudinal study on heahh and aging [ J ]. J Urul, 2013,189 ( 6 ) : 2208-2209. DOI : 10. 1016/j. juro. 2013.03. 013.
2Mobley D, Feibus A, Baum N. Benign prostatic hyperplasia and urinary symptoms: Evaluation and treatment [ J]. Postgrad Med, 2015, 127 ( 3 ) : 301-307. DOI: 10. 1080/00325481. 2015. 1018799.
3Lin J, Zhou J, Xu W, et al. Qianliening capsule treats benign prostatic hyperplasia via suppression of the EGF/STA33 signaling pathway[J]. ExpTher Med, 2013,5(5) :1293-1300. DOI: 10. 3892/etm. 2013. 1008.
4Stroup SP, Palazzi-Churas K, Kopp RP, et al. Trends in adverse events of benign prostatic: hyperplasia (BPH) in the USA, 1998 to 2008[J]. BJU lnt ,2012,109(1):84-87. DOI: 10. 1111/j. 1464-410X. 2011.
5刘婧,付小梅,吴建华,黄潇,关志宇.α_1-肾上腺素受体拮抗剂类药物治疗前列腺增生症的研究进展[J].中国医药科学,2014,4(13):38-43. 被引量：6
6Kaplan SA. Ursollc acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia [ J ]. J Urol,2013 ,89( 1 ) :388. DOI: 10. 1016/j. juro. 2012.09. 143.
7Titus MA, Li Y, Kozyreva OG, et al. 5ct-reductase type 3 enzyme in benign and malignant prostate [J]. Prostate ,2014,74 ( 3 ) :235- 249. DOI: 10. 1002/pros. 22745.
8Osman NI, Chapple CR, Cruz F, et al. Silodosin: a new subtype selective alpha-1 antagonist for the treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia[J]. Expert Opin Pharmacother ,2012,13 (14) : 2085-2096. DOI : 10. 1517/ 14656566. 2012. 714368.
9Levakov AF, Kaeanski MM, Vuckovie N, et al. The expression and localization of estrogen receptor beta in hyperplastic and neo- plastic prostate lesions. [ J ]. Vojnosanit Pregl, 2015,72 ( 10 ) : 906-913. DOI: 10.2298/VSP131022069F.
10Ngo T, Nicholas TJ, Chen J,et al. 5-HT1A receptor pharmacoph- ores to screen for off-target activity of α1-adrenoceptor antagonists [J]. J Comput Aided Mol Des, 2013,27(4):305-319. DOI: 10. 1007/s10822-013-9647-5.

二级参考文献43

1Toda N, Kaneko T, Kogen H. Development of an efficient therapeutic agent for Alzheimer's disease: design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter[J].Chem Pharm Bull ( Tokyo ), 2010, 58 ( 3 ) : 273-287.
2Hardy J.A hundred years of Alzheimer's disease research [J]. Neuron,2006,52 ( 1 ): 3-13.
3Morphy R, Rankovic Z.Designed multiple ligands. An emerging drug discovery paradigm[J].J Med Chem, 2005, 48 ( 21 ) : 6523-6543.
4Van der Schyf CJ, Geldenhuys WJ, Youdim MB.Multifunctional drugs with different CNS targets for neuropsychiatric disorders[J].J Neurochem, 2006,99 ( 4 ) : 1033-1048.
5Bica L, Crouch PJ, Cappai R, et al.Metallo-complex activation of neuroprotective signalling pathways as a therapeutic treatment for Alzheimer's disease[J].Mol Biosyst,2009,5 ( 2 ) : 134-142.
6Bolea I, Juarez-Jimenez J, de Los Rios C, et al. Synthesis, biological evaluation, and molecular modeling of donepezil and N-[ ( 5- ( benzyloxy ) -1-methyl-1H- indol-2-yl ) methyl]-N-methylprop-2-yn-l-amine hybrids as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer's disease[J].J Med Chem, 2011,54 ( 24 ): 8251-8270.
7Marco-Contelles J, Leon R, de Los Rios C, et al. Novel muhipotent tacrine- dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer's disease[J].J Med Chem, 2006,49 ( 26 ): 7607-7610.
8Toda N, Tako K, Marumoto S, et al.Design, synthesis and structure-activity relationships of dual inhibitors of acetyleholinesterase and serotonin transporter as potential agents for Alzheimer's disease[J].Bioorg Med Chem, 2003, 11 ( 9 ) : 1935-1955.
9Rosini M, Andrisano V, Bartolini M, et al.Rational approach to discover multipotent anti-Alzheimer drugs[J]. J Med Chem,2005,48 ( 2 ) : 360-363.
10Bolognesi ML, Cavalli A, Bergamini C, et al.Toward a rational design of muhitarget-directed antioxidants: merging memoquin and lipoic acid molecular frameworks[J].J Med Chem, 2009,52 ( 23 ) : 7883-7886.