摘要
背景:缺血早期脑组织损伤是急性脑卒中治疗面临的主要挑战。此期应用高压氧治疗是否对脑组织有明确的保护作用。目的:观察大鼠脑缺血再灌注后,高压氧诱导降钙素基因相关肽和β-内啡肽的动态变化以及高压氧治疗对其的影响,探讨高压氧的治疗作用。设计:随机对照实验。单位:首都医科大学动物科学部。材料:实验于2003-12/2005-02在首都医科大学动物科学部进行。选择清洁级雌性SD大鼠63只按随机数字表分为9组:假手术组7只;缺血再灌注组分别取再灌注6,24,48,96h时相点组,每组各7只;缺血再灌注+高压氧处理组分别取再灌注6,24,48,96h时相点组,每组各7只。干预:除假手术组外,其余各组建立脑缺血再灌注动物模型,夹闭双侧颈总动脉缺血20min后再通血流,假手术组同样手术,但不夹闭颈总动脉。假手术组和缺血再灌注组置于常压空气中,缺血再灌注+高压氧处理组治疗方案为:纯氧洗高压氧舱5min,升压5min,然后稳压在0.2MPa下吸纯氧45min,缓慢减压15min,出舱第1天在再灌注3h后行高压氧处理1次,以后均在3天同一时间作相同处理。缺血再灌注组和缺血再灌注+高压氧处理组分别于再灌注6,24,48,96h取血。主要观察指标:用放射免疫测定法测定各组血浆中降钙素基因相关肽和β-内啡肽的含量。结果:63只大鼠均进入结果分析。①缺血再灌注6h:高压氧组降钙素基因相关肽应激性升高(64.12±18.16)ng/L,出现时间较缺血再灌注组早,高于同时相点缺血再灌注组(32.62±11.72)ng/L和假手术组(49.09±8.59)ng/L(F=6.614,P<0.001,P<0.05);高压氧组β-内啡肽一过性增高。②缺血再灌注24h和48h:高压氧处理组降钙素基因相关肽从24h起即恢复至正常[(43.53±22.73)ng/L,F=0.390;(46.02±10.64)ng/L,F=0.969,P均>0.05]。③缺血再灌注96h:缺血再灌注组降钙素基因相关肽应激性(81.74±20.64)ng/L,高于假手术组(49.09±8.59)ng/L和同时相点高压氧组(40.98±20.52)ng/L(F=6.419,P<0.01);并明显高于6,24,48h的缺血再灌注组组(F=10.806,P均<0.01)。高压氧组β-内啡肽水平降至最低,明显低于假手术组[(370.00±130.15,872.30±403.92)ng/L,(F=3.691,P<0.05)]。结论:①早期高压氧治疗可通过升高血浆降钙素基因相关肽水平和降低β-内啡肽水平以减少梗死区的脑组织损伤。②随高压氧治疗次数的增多,其疗效更好。
BACKGROUND： Prevention of tissue damage during early hours of cerebral ischemia has remained a major challenge in acute stroke management. Whether the application of hyperbaric oxygen （HBO） can protect cerebral tissue or not remains a question to be answered.
OBJECTIVE： In cerebral ischemia-reperfusion rat model we studied the change on CGRP and β-endorphine levels and the therapeutic implication with hyperbaric oxygenation.
DESIGN： A randomized controlled animal study.
SETTING： Animal Research Department of Capital University of Medical Science.
MATERIALS： The experiment was carried out at the Animal Research Department of the Capital University of Medical Science from December 2003 to February 2005. Sixty three healthy Sprague-Dewey female rats were randomly divided into 9 groups. There were 7 in the sham operation group. Four groups with 7 in each groUp received cerebral ischemia followed by reperfusion （IR） and blood sample taken at 6, 24, 48 and 96 hour respectively. Another 4 groups （IR-HBO） with 7 in each received cerebral ischemia and reperfusion under hyperbaric oxgenation with blood sampling at 6, 24, 48 and 96 hours.
INTERVENTIONS： With the exception of sham operation groups, animals in all the experimental groups were exposed to global cerebral ischemia of 20 minutes duration. Sham operation group and the IR groups remained under the normal atmospheric pressure. The HBO chamber was flushed with 100% oxygen for 5 minutes and raised the pressure in 5 minutes to a steady pressure at 0.2MPa. Rats in IR-HBO groups were put into the chamber with inhalation of 100% oxygen for 45 minutes and decompression was done for 15 minutes. The rats in HBO group were placed into the HBO chamber after 3-hour post reperfusion on the first day and this treatment was repeated for three consecutive days, always at the same time. Plasma was collected after 6 hours, 24 hours, 48 hours or 96 hours post cerebral reperfusion, respectively.
MAIN OUTCOME MEASURES： The level of CGRP and β-EP in the plasma were measured by RIA （Radio-immunoassay）.
RESULTS： Sixty-three rots entered the final analysis. ① At 6-hour ischemia-repefusion： CGRP in HBO group was increased （64.12±18.16） ng/L and the onset time was earlier than that in IR group and the level was higher than those in IR group （32.62±11.72）ng/L and sham operation group （49.09±8.59）ng/L at the same time point （F=6.614, P 〈 0.001, P 〈 0.05）. β-EP level in 6-hour HBO group was slightly increased, but recovered at 24-hour, 48-hour, 96-hour HBO groups. ②At 24-hour and 48- hour ischemia-reperfusion： The plasma CGRP levels of the HBO group recover within 24-hours [（43.53±22.73）ng/L, F=0.390; （46.02±10.64）ng/L, F=0.969, P 〉 0.05]. ③ 96-hour ischemia-reperfusion： CGRP increase in the IR group （81.74±20.64）ng/L was higher than that in the sham operation group （49.09±8.59）ng/L and the HBO group （40.98±20.52）ng/L at the same time point （F=6.419, P 〈 0.01）; and also obviously higher than those in 6-hour, 24-hour and 48-hour IR group （F=10.806, P 〈 0.01）. The β-EP level at 96-hour HBO group was decreased to the lowest as compared with that in the sham operation group [（370.00±130.15）ng/L, （872.30±03.92）ng,,± F=3.691, P 〈 0.05].
CONCLUSION： ①HBO in the early period of cerebral ischemia can reduce the onset of injury of cerebral tissue through increasing CGRP level and decreasing β-EP level; ②The more times treated by HBO, the better is its therapeutic effect.
出处
《中国临床康复》
CSCD
北大核心
2006年第4期169-171,共3页
Chinese Journal of Clinical Rehabilitation
基金
北京市教委科技发展计划基金资助项目(KM200510025004)~~
