侧脑室注射Orexin-1受体拮抗剂对大鼠心血管效应的影响

目的:用侧脑室微量注射和免疫组化方法研究食欲素-1受体(OX1R)拮抗剂SB408124对麻醉大鼠的心血管效应及其作用机制。方法:雄性SD大鼠,侧脑室微量注射SB408124,及甲硝阿托品、六甲溴铵静脉注射预处理后侧脑室注射SB408124,观测动脉血压(MAP)和心率(HR)的变化。然后,用免疫组化方法检测侧脑室注射SB408124对大鼠脑延髓头端腹外侧区(RVLM)内酪氨酸羟化酶(TH)阳性神经元的影响。结果:侧脑室注射SB408124可显著降低麻醉大鼠的MAP和HR,但是HR变化不如MAP变化明显。应用六甲溴铵可完全阻断SB408124的心血管效应,但甲硝阿托品不能阻断SB408124的心血管效应。侧脑室注射SB408124可使鼠脑延髓头端腹外侧区内酪氨酸羟化酶阳性神经元的数量显著降低。结论:侧脑室注射OX1R拮抗剂SB408124可显著降低麻醉大鼠的MAP和HR,其作用主要是通过抑制交感神经系统的活性而实现的。

Cardiovascular effect of intracerebroventricular injection of orexin-1 receptor antagonist in rats

Objective： To study the cardiovascular effect of selective orexin-1 receptor （OX1 R） antagonist SB408124 in anesthetized rats and explore the underlying mechanism by using intracerebroventricular （ICV） microinjection combined with immunohistochemical assay. Methods： The changes of mean arterial blcxxt pressure （MAP） and heart rate （HR） of male Sprague-Dawley rats were recorded during ICV microinjection of SB408124 with or without pretreatment of atropine methyl nitrate or hexamethonium bromide. Furthermore, tyrosine hydroxylase（TH） immunopositive neurons in the rostral ventrolateral medulla（RVUVI） of the rat were detected with immunohistochemical assay after ICV microinjection of SB408124. Results： ICV adninistration of SB408124 resulted in a significant decrease in MAP in anesthetized rats, which was accompanied with a mild decrease in HR. The cardiovascular responses elicited by SIM08124 were not abolished by pretreatment of atropine methyl nitrate whereas fully abolished by pretreatment of hexamethonium bromide. The number of TH-immunopositive neurons in rat RVLM were significantly decreased following ICV administration of SB408124. Conclusion： ICV microinjection of selective OX1R antagonist SB408124 can cause decreases of MAP and HR mediated by inhibiting sympathetic activity in anesthetized rats.