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D1/D2 样多巴胺激动剂罗替高汀对帕金森病大鼠下尿路功能的作用机制。

Mechanisms of D1/D2-like dopaminergic agonist, rotigotine, on lower urinary tract function in rat model of Parkinson's disease.

机构信息

Department of Renal and Genitourinary Surgery, Graduate School of Medical Science, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

出版信息

Sci Rep. 2022 Mar 16;12(1):4540. doi: 10.1038/s41598-022-08612-3.

DOI:10.1038/s41598-022-08612-3
PMID:35296748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8927603/
Abstract

Parkinson's disease (PD) is a neurodegenerative condition caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. As activation of dopaminergic receptors is fundamentally involved in the micturition reflex in PD, the objective of this study was to determine the effect of a single dose of rotigotine ([-]2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin) on intercontraction interval (ICI) and voiding pressure (VP) in a rat model of PD. We used 27 female rats, PD was induced by injecting 6-hydroxydopamine (6-OHDA; 8 μg in 2 μL of 0.9% saline containing 0.3% ascorbic acid), and rotigotine was administrated at doses of 0.125, 0.25, or 0.5 mg/kg, either intravenous or subcutaneous injection. In rats with 6-OHDA-induced PD, intravenous injection of 0.25 or 0.5 mg/kg rotigotine led to a significantly lower ICI than after vehicle injection (p < 0.05). Additionally, VP was significantly lower in animals administered rotigotine compared to those injected with vehicle (p < 0.05). Compared to vehicle-injected animals, subcutaneous administration of rotigotine (0.125, 0.25, or 0.5 mg/kg) led to a significantly higher ICI at 2 h after injection (p < 0.05); however, there was no change in ICI after injection with (+)-SCH23390 hydrochloride. Dermal administration of rotigotine in a rat model of PD could suppress an overactive bladder.

摘要

帕金森病(PD)是一种由黑质致密部多巴胺能神经元丧失引起的神经退行性疾病。由于多巴胺受体的激活在 PD 的排尿反射中起着根本作用,因此本研究的目的是确定单剂量罗替戈汀([-]2-(N-丙基-N-2-噻吩乙基)-5-羟色胺)对帕金森病大鼠模型的间歇收缩间期(ICI)和排尿压(VP)的影响。我们使用了 27 只雌性大鼠,通过注射 6-羟多巴胺(6-OHDA;8μg 溶于 0.9%生理盐水,含 0.3%抗坏血酸)诱导 PD,并以 0.125、0.25 或 0.5mg/kg 的剂量静脉内或皮下给予罗替戈汀。在 6-OHDA 诱导的 PD 大鼠中,静脉内注射 0.25 或 0.5mg/kg 罗替戈汀导致 ICI 明显低于载体注射后(p<0.05)。此外,与给予载体的动物相比,给予罗替戈汀的动物的 VP 明显降低(p<0.05)。与给予载体的动物相比,皮下给予罗替戈汀(0.125、0.25 或 0.5mg/kg)在注射后 2 小时导致 ICI 显著升高(p<0.05);然而,在注射(+)-SCH23390 盐酸盐后,ICI 没有变化。在 PD 大鼠模型中,皮肤给予罗替戈汀可抑制逼尿肌过度活动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af4/8927603/90ab1236fad9/41598_2022_8612_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af4/8927603/0608b4d94b91/41598_2022_8612_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af4/8927603/90ab1236fad9/41598_2022_8612_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af4/8927603/0608b4d94b91/41598_2022_8612_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af4/8927603/90ab1236fad9/41598_2022_8612_Fig2_HTML.jpg

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Mov Disord Clin Pract. 2017 Apr 19;4(4):586-589. doi: 10.1002/mdc3.12488. eCollection 2017 Jul-Aug.
2
Long-term Outcome of Adenosine A2A Receptor Antagonist on Lower Urinary Tract Symptoms in Male Parkinson Disease Patients.腺苷A2A受体拮抗剂对男性帕金森病患者下尿路症状的长期疗效
Clin Neuropharmacol. 2018 May/Jun;41(3):98-102. doi: 10.1097/WNF.0000000000000281.
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New Frontiers of Basic Science Research in Neurogenic Lower Urinary Tract Dysfunction.
神经源性下尿路功能障碍基础科学研究的新前沿
Urol Clin North Am. 2017 Aug;44(3):491-505. doi: 10.1016/j.ucl.2017.04.014.
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Prevalence and treatment of LUTS in patients with Parkinson disease or multiple system atrophy.帕金森病或多系统萎缩患者的下尿路症状的患病率和治疗。
Nat Rev Urol. 2017 Feb;14(2):79-89. doi: 10.1038/nrurol.2016.254. Epub 2016 Dec 13.
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Role of the Anterior Cingulate Cortex in the Control of Micturition Reflex in a Rat Model of Parkinson's Disease.前扣带皮层在帕金森病大鼠模型排尿反射控制中的作用。
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Parkinson's disease.帕金森病。
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Br J Pharmacol. 2015 Feb;172(4):1124-35. doi: 10.1111/bph.12988. Epub 2015 Jan 13.
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