头部重点低温在全脑缺血再灌注中对NO过度产生的作用

The Effect of Selective Head Cooling on the Overproduction of Nitric Oxide during Global IschemicReperfusion

目的：在全脑缺血－再灌注后，尽早施行头部重点低温取得了较好的脑复苏效应。为阐明其机理，近１０年来，我院和各家兄弟单位研究表明头部重点低温脑复苏是通过多途径起作用的。基于近年来的研究发现，脑缺血后因脑组织ＮＯ明显升高，因而参与神经损伤。本研究意在观察低温对脑缺血再灌注后产生ＮＯ的效应，并探讨其可能机制。方法：ＳＤ大鼠６６只，均用腹腔麻醉，分为正常对照组（组Ⅰ），按Ｐｕｌｓｉｎｅｌｉ大鼠脑缺血模型制作的缺血对照组（组Ⅱ），常温再灌注组（组Ⅲ），头部重点低温再灌注组（组Ⅳ），给药（Ｌ－ＮＡＭＥ）组（组Ⅴ）。在完成实验条件后处死，用硝酸还原酶法测定脑组织ＮＯ３－／ＮＯ２－，另外用ＭＤＡ测定试剂盒检测ＭＤＡ含量，按Ｅｌｉｏｔ公式计算脑水含量。结果：缺血常温再灌注后，ＮＯ产生增多，ＭＤＡ和脑水含量相应增加，提示ＮＯ参与了再灌注损伤过程。头部重点低温不仅抑制再灌注ＮＯ的产生，也抑制ＭＤＡ和脑水含量增幅，而Ｌ－ＮＡＭＥ仅对ＮＯ有较强的抑制作用。结论：全脑缺血再灌注后ＮＯ大量升高，头部重点低温抑制ＮＯ产生有利于脑复苏作用。

ackground: Selective head cooling (SHC)may exert multifaceted benificial effects,both biochemically and histomorphologically,for brain resuscitation,as shown by animal experiments conducted in recent years.It ameliorates the neuronal ischemiareperfusion damage by inhibiting the release of toxic mediators and enhancing the recruitment of substances (e.g.Na+-K+ATPase) required for cellrepairing .Recently,it has been implied that overproduction of NO during cerebral ischemia may take part in neuronal damage.In order to explore the effect of SHC on NO production and its possible mechanism,this study was undertaken.Methods:66 SpragueDawley rats were allocated into normal control group(group Ⅰ),simple global ischemia group (groupⅡ),normothermic reperfusion group (group Ⅲ),SHC hypothermic reperfusion group (group Ⅳ)and LNAME treated reperfusion group (group Ⅴ).Group Ⅲ、Ⅳ、Ⅴ were divided further,according to the duration of reperfusion for 30、120 and 240min,into subgroups 1、2 and 3,with 6 rats in each subgroup.Global ischemia lasting 30 min was accomplished by Pulsinelli model.Rats were sacrificed and brain specimens were taken as requirements were fulfilled.Brain NO was measured in form of NO3-/NO2- by means of nitrate reductase method.Brain MDA was used to assay for radicals,according the method introduced by MDA box.Brain water content was calculated by Elliot method.Results:NO was overproduced during positischemic normothermic reperfusion,in association with rising of MDA and brain water content.Conclusion:NO takes part in the process of reperfusion damage.SHC not only attenuates the NO production,but also decreases the increments of MDA and brain water content,while LNAME has only the inhibitory effect on NO production.NO is overproduced during postischemic normothermic reperfusion.SHC seems to be effective to ameliorate the reperfusion damage,thus favorable for brain resuscitation.