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五淋散与山楂联用通过抑制中性粒细胞NADPH氧化酶活性改善P物质诱导的膀胱过度活动症。

Combination of Wu Lin San and Shan Zha ameliorates substance P-induced hyperactive bladder via the inhibition of neutrophil NADPH oxidase activity.

作者信息

Chen Wang-Chuan, Shih Chun-Chuan, Lu Wan-An, Li Ping-Chia, Chen Chau-Jong, Hayakawa Satoshi, Shimizu Kazufumi, Chien Chiang-Ting

机构信息

Department of Traditional Chinese Medicine, Ren-Ai Branch, Taipei City Hospital, Taipei, and Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan.

出版信息

Neurosci Lett. 2006 Jul 10;402(1-2):7-11. doi: 10.1016/j.neulet.2006.03.037. Epub 2006 Apr 24.

DOI:10.1016/j.neulet.2006.03.037
PMID:16632195
Abstract

Substance P (SP) via neurokinin type 1 receptor activates leukocytes to produce burst release of reactive oxygen species (ROS) and increases leukocytes adhesion to the vessels in the inflamed bladder. Activation of neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity may contribute to the neutrophil ROS production. We explored the therapeutic effect of traditional Chinese formula for urinary dysfunction, Wu Lin San (WLS), and a modified formula WLS plus Shan Zha (WLSSZ) on SP-induced bladder hyperactivity. We evaluated WLS, Shan Zha, and WLSSZ effect on neutrophils NADPH oxidase activity in SP-stimulated neutrophils in vitro, and isovolumetric cystometrogram and ROS activity in vivo in anesthetized rat bladder with SP stimulation. Our results showed that WLS, Shan Zha, and WLSSZ inhibited SP-induced NADPH oxidase activity in an order WLSSZ>Shan Zha>WLS. Exogenous SP enhanced systemic vasodilation, bladder hyperactivity and bladder ROS. One week of oral administration of WLS or WLSSZ significantly reduced SP-induced bladder ROS amount and leukocyte accumulation and ameliorated the hyperactive bladder response. The therapeutic action was better in WLSSZ than in WLS. Our results indicate that a modified formula Wu Lin San plus Shan Zha can potentially ameliorate SP-induced neurogenic inflammation possibly via the inhibition of leukocyte NADPH oxidase activity.

摘要

P物质(SP)通过1型神经激肽受体激活白细胞,使其产生活性氧(ROS)的爆发性释放,并增加白细胞在炎症膀胱中与血管的黏附。中性粒细胞烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活性的激活可能有助于中性粒细胞产生ROS。我们探讨了治疗排尿功能障碍的中药方剂五淋散(WLS)以及改良方剂五淋散加山楂(WLSSZ)对SP诱导的膀胱活动亢进的治疗作用。我们在体外评估了WLS、山楂和WLSSZ对SP刺激的中性粒细胞中中性粒细胞NADPH氧化酶活性的影响,并在体内对麻醉大鼠膀胱进行SP刺激时评估了等容膀胱测压和ROS活性。我们的结果表明,WLS、山楂和WLSSZ抑制SP诱导的NADPH氧化酶活性的顺序为WLSSZ>山楂>WLS。外源性SP增强了全身血管舒张、膀胱活动亢进和膀胱ROS。口服WLS或WLSSZ一周可显著降低SP诱导的膀胱ROS量和白细胞积聚,并改善膀胱活动亢进反应。WLSSZ的治疗作用优于WLS。我们的结果表明,改良方剂五淋散加山楂可能通过抑制白细胞NADPH氧化酶活性来潜在地改善SP诱导的神经源性炎症。

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