Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats.

Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats.
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DOI:
10.1016/j.freeradbiomed.2012.12.015
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发表时间:
2013-04
影响因子:
7.4
通讯作者:
Wang, Songlin
Wang, Songlin
中科院分区:
医学1区
文献类型:
--
作者:
Jin, Luyuan;Qin, Lizheng;Xia, Dengsheng;Liu, Xibao;Fan, Zhipeng;Zhang, Chunmei;Gu, Liankun;He, Junqi;Ambudkar, Indu S.;Deng, Dajun;Wang, Songlin

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血液中高达25%的循环硝酸盐被唾液腺主动吸收、浓缩并分泌到唾液中。唾液中的硝酸盐在口腔或胃内可被肠道细菌还原为亚硝酸盐,在体内进一步转化为一氧化氮(NO),可能起到胃保护作用。然而,唾液硝酸盐是否在人体内积极分泌尚未确定。本研究旨在确定唾液硝酸盐是否作为急性应激反应在人体中积极分泌,以及唾液硝酸盐在应激诱导的胃损伤中起什么作用。为观察应激状态下唾液硝酸盐功能的变化,对22名健康志愿者进行了从68 m高处跳下的强烈应激活动前后唾液硝酸盐和亚硝酸盐的变化进行了分析。分析了一系列应力指标,以监测应力状况。结果发现,志愿者在跳跃后即刻混合唾液中硝酸盐浓度和总量均显著增加,并在1h后进一步增加(p < 0.01)。唾液亚硝酸盐在跳跃后立即达到最大值,并在1 h后维持。为了研究唾液硝酸盐和亚硝酸盐在应激保护中的生物学功能,我们进一步在双侧腮腺和下颌下导管结扎(BPSDL)的雄性成年大鼠中进行了水浸束缚应激(WIRS)试验。胃内硝酸盐,亚硝酸盐和NO;胃粘膜血流量;和胃溃疡指数(UI)进行了监测,并在饮用水中给予硝酸盐,以补偿BPSDL动物的硝酸盐分泌。与假手术对照组大鼠相比,BPSDL大鼠胃内硝酸盐、亚硝酸盐和NO水平以及胃粘膜血流量显著降低(p < 0.05)。硝酸盐给药后,在BPSDL大鼠中观察到恢复。WIRS诱导的UI在BPSDL动物中显著高于对照组,硝酸盐给药挽救了WIRS诱导的BPSDL大鼠胃损伤。总之,本研究表明,应激促进唾液硝酸盐的分泌和亚硝酸盐的形成,这可能通过硝酸盐依赖的NO途径在胃保护对抗应激诱导的损伤中发挥重要作用。
Up to 25% of the circulating nitrate in blood is actively taken up, concentrated, and secreted into saliva by the salivary glands. Salivary nitrate can be reduced to nitrite by the commensal bacteria in the oral cavity or stomach and then further converted to nitric oxide (NO) in vivo, which may play a role in gastric protection. However, whether salivary nitrate is actively secreted in human beings has not yet been determined. This study was designed to determine whether salivary nitrate is actively secreted in human beings as an acute stress response and what role salivary nitrate plays in stress-induced gastric injury. To observe salivary nitrate function under stress conditions, alteration of salivary nitrate and nitrite was analyzed among 22 healthy volunteers before and after a strong stress activity, jumping down from a platform at the height of 68m. A series of stress indexes was analyzed to monitor the stress situation. We found that both the concentration and the total amount of nitrate in mixed saliva were significantly increased in the human volunteers immediately after the jump, with an additional increase 1 h later (p < 0.01). Saliva nitrite reached a maximum immediately after the jump and was maintained 1 h later. To study the biological functions of salivary nitrate and nitrite in stress protection, we further carried out a water-immersion-restraint stress (WIRS) assay in male adult rats with bilateral parotid and submandibular duct ligature (BPSDL). Intragastric nitrate, nitrite, and NO; gastric mucosal blood flow; and gastric ulcer index (UI) were monitored and nitrate was administrated in drinking water to compensate for nitrate secretion in BPSDL animals. Significantly decreased levels of intragastric nitrate, nitrite, and NO and gastricmucosal blood flow were measured in BPSDL rats during the WIRS assay compared to sham control rats (p < 0.05). Recovery was observed in the BPSDL rats upon nitrate administration. The WIRS-induced UI was significantly higher in the BPSDL animals compared to controls, and nitrate administration rescued the WIRS-induced gastric injury in BPSDL rats. In conclusion, this study suggests that stress promotes salivary nitrate secretion and nitrite formation, which may play important roles in gastric protection against stress-induced injury via the nitrate-dependent NO pathway.
DOI: 10.1093/cvr/cvq366
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