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广藿香醇对大鼠海绵体的舒张作用及其机制

Relaxation Effect of Patchouli Alcohol in Rat Corpus Cavernous and Its Underlying Mechanisms.

作者信息

Chen Fangjun, Xu Yifei, Wang Jing, Yang Xufeng, Cao Hongying, Huang Ping

机构信息

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.

Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China.

出版信息

Evid Based Complement Alternat Med. 2020 Feb 28;2020:3109069. doi: 10.1155/2020/3109069. eCollection 2020.

DOI:10.1155/2020/3109069
PMID:32190080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7066398/
Abstract

In this study, we investigated the relaxation effect and mechanisms of patchouli alcohol (PA) on rat corpus cavernosum. Corpus cavernosum strips were used in organ baths for isometric tension studies. The results showed that PA demonstrated concentration-dependent relaxation effect on rat corpus cavernosum. The relaxant response to PA was not influenced by tetrodotoxin and atropine while it was significantly inhibited by removal of endothelium. L-N-nitroarginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor) significantly inhibited relaxation response to PA, whereas indomethacin (COX inhibitor) had no effect on PA-induced relaxation. The treatment of endothelium-deprived corpus cavernosum with several potassium channel blockers including tetraethylammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide had no effect on PA-induced relaxation. Endothelium-deprived corpus cavernosal contractions induced by cumulative addition of Ca to high KCl solution without CaCl were significantly inhibited by PA. Also, PA improved relaxant capacity of sildenafil in rat corpus cavernosum. In addition, the perfusion with PA significantly increased the levels of cGMP and expression of mRNA and protein of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, intracavernous injection of PA enhanced the rise in intracavernous pressure in rats during cavernosal nerve electric stimulation. In conclusion, PA relaxed the rat corpus cavernosum attributed to both endothelium-dependent and -independent properties. While the former component was mostly involved in nitric oxide signaling pathway, the endothelium-independent mechanism involved in PA-induced relaxation was probably linked to calcium antagonism.

摘要

在本研究中，我们研究了广藿香醇（PA）对大鼠海绵体的舒张作用及其机制。采用海绵体条在器官浴槽中进行等长张力研究。结果表明，PA对大鼠海绵体具有浓度依赖性舒张作用。PA的舒张反应不受河豚毒素和阿托品的影响，但去除内皮后则受到显著抑制。L-硝基精氨酸甲酯（L-NAME，一种一氧化氮合酶抑制剂）或1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ，一种可溶性鸟苷酸环化酶抑制剂）显著抑制了对PA的舒张反应，而吲哚美辛（COX抑制剂）对PA诱导的舒张无影响。用几种钾通道阻滞剂（包括四乙铵（TEA）、4-氨基吡啶（4-AP）和格列本脲）处理去内皮的海绵体对PA诱导的舒张无影响。在无氯化钙的高钾溶液中累积添加钙诱导的去内皮海绵体收缩被PA显著抑制。此外，PA提高了西地那非对大鼠海绵体的舒张能力。另外，PA灌注显著增加了cGMP水平以及神经元型一氧化氮合酶（nNOS）和内皮型一氧化氮合酶（eNOS）的mRNA和蛋白表达。此外，海绵体内注射PA增强了海绵体神经电刺激期间大鼠海绵体内压的升高。总之，PA使大鼠海绵体舒张，这归因于内皮依赖性和非依赖性特性。前者主要参与一氧化氮信号通路，而PA诱导舒张的内皮非依赖性机制可能与钙拮抗作用有关。

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