糖尿病大鼠尿道α1肾上腺素能受体与神经生长因子表达的改变及其对尿道功能的影响

doi:10.6040/j.issn.1671-7554.0.2015.581

摘要/Abstract

摘要： 目的探讨糖尿病大鼠尿道α1肾上腺素能受体与神经生长因子(NGF)表达的改变及其对尿道功能的影响。方法 20只雌性Wistar大鼠随机分为正常对照组(10只)和糖尿病组(10只)。采用尿流动力学方法检测大鼠膀胱与尿道压力;RT-qPCR与Western blotting测定两组大鼠尿道中α1肾上腺素能受体的表达;RT-qPCR与ELISA法测定两组大鼠尿道中NGF的表达。Western blotting测定两组大鼠尿道中NGF前体(proNGF)、P75神经营养因子受体(P75^NTR)及 Sortilin的表达水平。结果与对照组比较,糖尿病组大鼠尿道舒张时的最低尿道灌注压增高;静脉注射α1肾上腺素能受体拮抗剂(盐酸坦索罗辛)可降低糖尿病大鼠的最低尿道灌注压以及尿道灌注压的基线水平。RT-qPCR与Western blotting结果显示,糖尿病组大鼠尿道α1a 和α1d受体表达水平升高(P<0.05)。RT-qPCR与ELISA结果显示,糖尿病组大鼠尿道NGF的表达明显减少。Western blotting结果显示,糖尿病组大鼠proNGF的表达升高(P<0.05)、大鼠尿道中P75^NTR表达减少(P<0.05),两组比较Sortilin的表达差异无统计学意义(P>0.05)。结论糖尿病大鼠尿道中α1肾上腺能受体表达水平的升高以及NGF/proNGF通路的改变可能是导致糖尿病尿道功能紊乱的机制。

关键词: 尿道, 神经生长因子, 大鼠, 糖尿病, α1肾上腺素能受体

Abstract: Objective To explore the changes on the expressions of α1-adrenergic receptor and nerve growth factor (NGF) and theirs effects on the urethral function in diabetic rats. Methods A total of 20 female Wistar rats were randomly divided into 2 groups. Urethral function was examined by detecting the bladder pressure and urethral perfusion pressure (UPP). The expressions of α1-adrenergic receptor and NGF in the urethra were measured with RT-qPCR and ELISA. The expressions of proNGF, P75^NTR and Sortilinin in the urethra were evaluated with Western blotting. Results The lowest urethral pressure (UPP nadir) during urethral relaxation was higher in diabetic rats. The UPP nadir and baseline UPP in diabetic rats was significantly decreased by intravenous administration of α1-adrenoceptor antagonist (tamsulosin). The α1a and α1d adrenergic receptor in the urethra of the diabetic group was significantly increased as detected with RT-qPCR and Western blotting (P<0.05). RT-qPCR and ELISA studies showed a significant decrease of NGF, and Western blotting indicated a significant increase of proNGF (P<0.05). There was a statistical decrease of P75^NTR in the urethra of diabetic rats (P<0.05), but no significant difference concerning Sortilin between the two groups (P>0.05). Conclusion The increase in the expression of α1-adrenoceptor and changes of NGF/ProNGF pathway in diabetic rats is a possible mechanism of diabetic urethral dysfunction.

Key words: α1-adrenoceptor, Rats, Urethra, Diabetes mellitus, Nerve growth factor

中图分类号:

R695

张东青, 王勇, 陈守臻, 朱耀丰, 史本康. 糖尿病大鼠尿道α1肾上腺素能受体与神经生长因子表达的改变及其对尿道功能的影响[J]. 山东大学学报（医学版）, 2015, 53(9): 30-34.

ZHANG Dongqing, WANG Yong, CHEN Shouzhen, ZHU Yaofeng, SHI Benkang. Changes on the expressions of alpha1-adrenergic receptor and nerve growth factor and their effects on urethral function in diabetic rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(9): 30-34.

参考文献

[1] Yuan Z, Tang Z, He C, et al. Diabetic cystopathy: a review[J]. J Diabetes, 2015, 7(4):442-447.
[2] Arrellano-Valdez F, Urrutia-Osorio M, Arroyo C, et al. A comprehensive review of urologic complications in patients with diabetes[J]. Springerplus, 2014, 23(3):549. doi:10.1186/2193-1801-3-549. eCollection, 2014.
[3] James R, Hijaz A. Lower urinary tract symptoms in women with diabetes mellitus: a current review[J]. Curr Urol Rep, 2014, 15(10):440. doi:10.1007/s11934-014-0440-3.
[4] Liu G, Lin YH, Yamada Y, et al. External urethral sphincter activity in diabetic rats[J]. Neurourol Urodyn, 2008, 27(5):429-434.
[5] Smith PG, Warn JD, Steinle JJ, et al. Modulation of parasympathetic neuron phenotype and function by sympathetic innervation [J]. Auton Neurosci, 2002, 96(1):33-42.
[6] Bradshaw RA, Pundavela J, Biarc J, et al. NGF and ProNGF: regulation of neuronal and neoplastic responses through receptor signaling [J]. Adv Biol Regul, 2015, 58:16-27. doi:10.1016/j.jbior.2014.11.003. Epub 2014 Nov 20.
[7] Lebrun-Julien F, Bertrand MJ, De Backer O, et al. ProNGF induces TNFalpha-dependent death of retinal ganglion cells through a P75^NTR non-cell-autonomous signaling pathway[J]. Proc Natl Acad Sci U S A, 2010, 107(8):3817-3822.
[8] Torimoto K, Hirao Y, Matsuyoshi H, et al. alpha1-Adrenergic mechanism in diabetic urethral dysfunction in rats[J]. J Urol, 2005, 173(3):1027-1032.
[9] Torimoto K, Fraser MO, Hirao Y, et al. Urethral dysfunction in diabetic rats [J]. J Urol, 2004, 171(5):1959-1964.
[10] 卫重娟, 程焱, 梁浩, 等. 神经生长因子对糖尿病神经病变大鼠神经肽和神经传导速度的影响[J]. 中华神经医学杂志, 2013, 12(8):779-782. WEI Chongjuan, CHENG Yan, LIANG Hao, et al. Influence of nerve growth factor in neuropeptides and nerve conduction velocity in rats with experimental diabetic peripheral neuropathy[J]. Chin J Neuromed, 2013,12(8):779-782.
[11] Hellweg R, Raivich G, Hartung HD, et al. Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in experimental diabetic neuropathy[J]. Exp Neurol, 1994, 130(1):24-30.
[12] Goins WF, Yoshimura N, Phelan MW, et al. Herpes simplex virus mediated nerve growth factor expression in bladder and afferent neurons: potential treatment for diabetic bladder dysfunction[J]. J Urol, 2001, 165(5):1748-1754.
[13] Li Y, Shi B, Wang D, et al. Nerve growth factor and substance P: expression in a rat model of diabetic bladder[J]. Int Urol Nephrol, 2011, 43(1):109-116.
[14] Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system[J]. Curr Opin Neurobiol, 2000, 10(3):381-391.
[15] Hata T, Sakata N, Yoshimatsu G, et al. Nerve growth factor improves survival and function of Transplanted islets via TrkA-mediated β cell proliferation and revascularization[J]. Transplantation, 2015, 99(6):1132-1143.
[16] Wehrman T, He X, Raab B, et al. Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors[J]. Neuron, 2007, 53(1):25-38.
[17] Meeker RB, Williams KS.The p75 neurotrophin receptor: at the crossroad of neural repair and death[J]. Neural Regen Res, 2015, 10(5):721-725.
[18] Petrie CN, Armitage MN, Kawaja MD. Myenteric expression of nerve growth factor and the p75 neurotrophin receptor regulate axonal remodeling as a consequence of colonic inflammation in mice[J]. Exp Neurol, 2015, 271:228-240. doi:10.1016/j.expneurol.2015.06.010. [Epub ahead of print]
[19] Nykjaer A, Willnow TE. Sortilin: a receptor to regulate neuronal viability and function[J]. Trends Neurosci, 2012, 35(4):261-270.
[20] Baglole CJ, Sigalet DL, Martin GR, et al. Acute denervation alters the epithelial response to adrenoceptor activation through an increase in alpha1-adrenoceptor expression on villus enterocytes[J]. Br J Pharmacol, 2006, 147(1):101-108.

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