Changes in Alpha1-Adrenoceptor and NGF/proNGF Pathway: A Possible Mechanism in Diabetic Urethral Dysfunction

Changes in Alpha1-Adrenoceptor and NGF/proNGF Pathway: A Possible Mechanism in Diabetic Urethral Dysfunction
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DOI:
10.1159/000355711
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发表时间:
2014-01-01
影响因子:
1.6
通讯作者:
Shi, Benkang
Shi, Benkang
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Shouzhen;Zhu, Yaofeng;Shi, Benkang

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目的:探讨糖尿病诱导后尿道α 1-肾上腺素能受体及神经生长因子(NGF)/NGF前体(proNGF)通路的变化。材料与方法:采用同步记录糖尿病大鼠等容条件下膀胱内压和尿道灌注压(UPP)测定尿道舒张功能。采用实时定量聚合酶链式反应(RT-qPCR)、酶联免疫吸附法和Western blotting检测大鼠尿道α - 1-肾上腺素受体、NGF、proNGF、神经营养因子低亲和力p75受体(p75(NTR))和sortilin的表达。结果:糖尿病大鼠尿道舒张时尿道最低压(UPP最低点)明显增高。静脉注射坦索罗辛,一种α - 1肾上腺素受体拮抗剂,显著降低糖尿病大鼠的UPP最低点和基线UPP。RT-qPCR和Western blotting研究显示,糖尿病组尿道中α 1a-和α 1b-肾上腺素受体的表达有统计学意义(p
Objective:To investigate the changes in the alpha 1-adrenoceptor and nerve growth factor (NGF)/NGF precursor (proNGF) pathway in the urethra after diabetes induction. Materials and Methods: Urethral relaxation function was determined by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) in diabetic rats. The expression of alpha 1-adrenoceptor, NGF, proNGF, low-affinity p75 receptor for neurotrophins (p75(NTR)) and sortilin in the urethras was measured using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay and Western blotting. Results: In diabetic rats, the lowest urethral pressure (UPP nadir) during urethral relaxation was significantly higher. Intravenous administration of tamsulosin, an alpha 1-adrenoceptor antagonist, significantly decreased the UPP nadir and baseline UPP in diabetic rats. RT-qPCR and Western blotting studies showed a statistically significant increase of alpha 1a- and alpha 1b-adrenoceptor in the urethras from the diabetic group (p