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首页> 外文期刊>American Journal of Physiology >Role of nitric oxide in hepatic microvascular injury elicited by acetaminophen in mice.
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Role of nitric oxide in hepatic microvascular injury elicited by acetaminophen in mice.

机译：一氧化氮在对乙酰氨基酚引起的小鼠肝微血管损伤中的作用。

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摘要

Nitric oxide (NO) is suggested to play a role in liver injury elicited by acetaminophen (APAP). Hepatic microcirculatory dysfunction also is reported to contribute to the development of the injury. As a result, the role of NO in hepatic microcirculatory alterations in response to APAP was examined in mice by in vivo microscopy. A selective inducible NO synthase (iNOS) inhibitor,l-N6-(1-iminoethyl)-lysine (L-NIL), or a nonselective NOS inhibitor, NG-nitro-l-arginine methyl ester (L-NAME), was intraperitoneally administered to animals 10 min before APAP gavage. L-NIL suppressed raised alanine aminotransferase (ALT) values 6 h after APAP, whereas L-NAME increased those 1.7-fold. Increased ALT levels were associated with hepatic expression of iNOS. L-NIL, but not L-NAME, reduced the expression. APAP caused a reduction (20%) in the numbers of perfused sinusoids. L-NIL restored the sinusoidal perfusion, but L-NAME was ineffective. APAP increased the area occupied by infiltrated erythrocytes into the extrasinusoidal space. L-NIL tended to minimize this infiltration, whereas L-NAME further enhanced it. APAP caused an increase (1.5-fold) in Kupffer cell phagocytic activity. This activity in response to APAP was blunted by L-NIL, whereas L-NAME further elevated it. L-NIL suppressed APAP-induced decreases in hepatic glutathione levels. These results suggest that NO derived from iNOS contributes to APAP-induced parenchymal cell injury and hepatic microcirculatory disturbances. L-NIL exerts preventive effects on the liver injury partly by inhibiting APAP bioactivation. In contrast, NO derived from constitutive isoforms of NOS exerts a protective role in liver microcirculation against APAP intoxication and thereby minimizes liver injury.
机译：一氧化氮（NO）被认为在对乙酰氨基酚（APAP）引起的肝损伤中起作用。据报道，肝微循环功能障碍也导致了损伤的发展。结果，通过体内显微镜检查了小鼠中NO在响应APAP的肝微循环改变中的作用。腹膜内注射选择性诱导型NO合酶（iNOS）抑制剂1-N6-（1-亚氨基乙基）-赖氨酸（L-NIL）或非选择性NOS抑制剂NG-硝基-1-精氨酸甲酯（L-NAME）在APAP管饲前10分钟向动物给药。 L-NIL抑制APAP后6小时升高的丙氨酸转氨酶（ALT）值，而L-NAME则将其升高1.7倍。 ALT水平升高与iNOS的肝表达有关。 L-NIL但不是L-NAME简化了表达式。 APAP导致灌注的正弦曲线数量减少（20％）。 L-NIL恢复了正弦灌注，但L-NAME无效。 APAP增加了浸润的红细胞进入窦外间隙的面积。 L-NIL倾向于使这种渗透最小化，而L-NAME则进一步增强了这种渗透。 APAP导致库普弗细胞吞噬活性增加（1.5倍）。响应APAP的这种活动被L-NIL削弱了，而L-NAME进一步升高了它。 L-NIL抑制了APAP诱导的肝谷胱甘肽水平降低。这些结果表明，来自iNOS的NO有助于APAP诱导的实质细胞损伤和肝微循环障碍。 L-NIL可以通过抑制APAP的生物活化来部分地预防肝损伤。相反，源自NOS组成型亚型的NO在肝微循环中发挥抗APAP中毒的保护作用，从而最大程度地减少了肝损伤。

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