芳香开窍药对脑缺血再灌注损伤大鼠保护作用机制的研究

Protective mechanism of aromatic resuscitation drugs in cerebral ischemia-reperfusion injury model rats

目的:研究麝香、冰片、安息香和苏合香四味芳香开窍药对脑缺血再灌注损伤大鼠的保护作用机制。方法:线栓法制备局灶性脑缺血再灌注损伤大鼠模型,观察药物对大鼠术前、缺血2h再灌注4h、10h、22h时体温的影响;比色法测定大鼠缺血2h再灌注22h后血清NO含量与NOS活性;ELISA法测定缺血侧脑组织中IL-1β和IL-6含量。结果:冰片(0.2g/kg)能明显抑制大鼠缺血2h再灌注4h、10h、22h时体温的异常升高,麝香(66.6mg/kg)和苏合香(1.332g/kg)仅在再灌注后4h时明显抑制体温升高,安息香(1.0g/kg)作用不明显。麝香、冰片和苏合香能显著降低模型动物血清NO含量,麝香、冰片还能显著抑制血清NOS活性。冰片、麝香能显著降低缺血侧脑组织IL-1β、IL-6含量,苏合香和安息香的作用不明显。结论:芳香开窍药对脑缺血再灌注损伤大鼠有一定的保护作用,其中麝香、冰片作用为优,其次苏合香,安息香作用较弱,作用机制可能与抑制炎症介质释放减轻炎症损伤及抗NO神经毒性有关。冰片对模型动物体温升高的良好抑制作用,从一个侧面反映了该药区别于其他三味药物的"寒凉"之性。

Objective： To study the protective mechanism of four aromatic resuscitation drugs（moschus,borneolum,benzoinum,styrax） on cerebral ischemia-reperfusion injury in rats.Methods： Focal middle cerebral artery occlusion（MCAO） model was made by suture-occluded method.The rectal temperature of rats was observed on preoperative and reperfusion 4h,10h,22h after ischemia 2h.After 22h reperfusion,all animals were decapitated.The content of NO and NOS activity in serum were measured by chromatometry,and the content of IL-1β and IL-6 in ischemia side brain tissue were measured by ELISA.Results： Borneolum（0.2g/kg）significantly inhibited abnormal increase of rectal temperature after reperfusion 4h,10h,22h in model rats,while moschus（66.6mg/kg）and styrax（1.332g/kg）showed significant inhibition after reperfusion 4h and benzoinum（1.0g/kg）showed no effect at all time point.moschus,borneolum and styrax significantly decreased the content of NO in serum in model rats,and moschus and borneolum also inhibited NOS activity in model rat＇s serum.Moschus and borneolum significantly reduced the level of IL-1β and IL-6 in ischemia side brain tissue,while styrax and benzoinum had no significant effect on them.Conclusions： Aromatic resuscitation drugs have protective effect on cerebral ischemia-reperfusion injury in rats,which the effects of borneolum and moschus are better than styrax.But the effect of benzoinum is inferior to them.The protective mechanism of aromatic resuscitation drugs are partly due to its functions of inhibiting inflammation mediators releasing and anti-neurotoxicity of NO.In addition,significant inhibition of borneolum on abnormal increase of temperature in model rats reflects the difference in nature of herb among this four drugs,which outstands the ＂cool＂ nature of borneolum.