川芎嗪对缺氧所致大鼠呼吸效应和脑干神经元型一氧化氮合酶表达的影响

Effect of tetramethylpyrazine on the responses of respiration and expression of nNOS in brainstem to hypoxia in rats

本文旨在研究川芎嗪对缺氧引起的呼吸变化和脑干神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)表达的影响。用吸入8%O2+92%N2的方法引起大鼠全身性缺氧,以膈肌放电作为指标,动态观察呼吸活动的变化;用免疫组织化学的方法观察脑干中nNOS表达的变化。在缺氧组大鼠,缺氧20 min时,呼吸活动受到显著抑制,表现为吸气时程缩短,呼气时程延长,呼吸频率减慢和吸气幅度降低(P<0.05);在川芎嗪预处理组大鼠,缺氧未引起呼吸抑制(P>0.05)。缺氧时,延髓腹外侧网状核、斜方体核、舌下神经核和面神经核的nNOS表达增加(P<0.05);川芎嗪预处理组大鼠上述核团的nNOS的表达均进一步增加(P<0.05)。结果表明,川芎嗪对缺氧引起的呼吸抑制有对抗作用,nNOS可能参与了这一过程。

The aim of the present study was to investigate the effect of tetramethylpyrazine (TMP) on the changes of respiration and expression of neuronal nitric oxide synthase (nNOS) in brainstem induced by hypoxia in the rats. Hypoxia was induced by inhalation of 8% O2-balanced N,.The electromyogram (EMG) of diaphragm was monitored to evaluate the respiratory response of the rats to hypoxia. The immunohistochemical staining technique was used to study the change of the expression of nNOS in the brainstem during hypoxia. In the rats of hypoxia group, a successive process of response, excitatory followed by inhibitory, was produced. Twenty min after hypoxia, a significant inhibition of respiration occurred, which was characterized with a marked decrease in the inspiratory duration, the respiratory frequency, and the amplitude of inspiration and a prolongation of expiratory duration (P<0.05). In the rats of pretreated with TMP, the respiratory activity was not obviously depressed (P>0.05). In the rats of hypoxia group, the level of nNOS immunoreactivity was enhanced remarkably in the lateral reticular nucleus, nucleus of trapezoid, hypoglossal nucleus and the facial nucleus compared with the control group (P<0.05). In the rats of pretreated with TMP, the nNOS level increased further in the nuclei mentioned above (P<0.05). The results obtained indicate that TMP can reverse the inhibitory effect of hypoxia on respiration in the rats and that nNOS may be involved in the respiratory protective action of TMP.