CAJ | 학술논문

目的评价联合应用缺血后处理、远隔缺血后处理和纳洛酮后处理对大鼠局灶性脑缺血-再灌注损伤的影响.方法将110只大鼠随机分为5组(n=22),通过阻塞右侧大脑中动脉90 min和再灌注24 h实施局灶性脑缺血.再灌注.Ⅰ组为对照组;Ⅱ组为缺血后处理组,再灌注开始时实施3次30 s的缺血和再灌注;Ⅲ组为远隔缺血后处理组,再灌注开始前实施5 min的右侧股动脉缺血;Ⅳ组为纳洛酮后处理组,再灌注开始时腹腔注射纳洛酮10 mg/kg;Ⅴ组为联合应用组.再灌注2 h和24 h时测定大鼠的神经功能障碍评分(NDS);再灌注24 h时,测定脑梗死区面积(n=10)、脑组织微管相关蛋白2(MAP2)表达(n=6)和脑组织血浆容量、血管直径和节段长度(n=6).结果观察期所有时间点的心率和平均动脉压(MAP)组间比较差异均无统计学意义(均P＞0.05).再灌注24 h后,Ⅰ～Ⅴ组的缺血侧脑梗死面积与同侧大脑半球面积的比值(即脑梗死严重程度)分别是43%±6%、31%±4%、32%±5%、28%±6%和21%±7%.与Ⅰ组比较,Ⅱ～Ⅴ组的NDS和脑梗死严重程度均低(均P＜0.05),MAP2表达、血浆容量、血管直径和节段长度均高,但上述指标在Ⅱ组、Ⅲ组和Ⅵ组之间比较差异均无统计学意义(均P＞0.05).与Ⅰ组、Ⅱ组、Ⅲ组和Ⅳ组比较,Ⅴ组的NDS评分和脑梗死程度均低(均P＜0.05),MAP2表达和血浆容量显著高(均P＜0.05),但是缺血侧脑组织的血管直径和节段长度在Ⅱ组、Ⅲ组Ⅵ组和Ⅴ组之问差异均无统计学意义(均P＞0.05).结论在局灶性脑缺血-再灌注损伤大鼠,缺血后处理、远隔缺血后处理和纳洛酮后处理均具有明显的神经保护作用,表现为脑梗死严重程度降低和神经功能障碍改善.联合应用3种后处理措施可获得增强的神经保护效应.
목적 평개연합응용결혈후처리、원격결혈후처리화납락동후처리대대서국조성뇌결혈-재관주손상적영향.방법 장110지대서수궤분위5조(n=22),통과조새우측대뇌중동맥90 min화재관주24 h실시국조성뇌결혈.재관주.Ⅰ조위대조조;Ⅱ조위결혈후처리조,재관주개시시실시3차30 s적결혈화재관주;Ⅲ조위원격결혈후처리조,재관주개시전실시5 min적우측고동맥결혈;Ⅳ조위납락동후처리조,재관주개시시복강주사납락동10 mg/kg;Ⅴ조위연합응용조.재관주2 h화24 h시측정대서적신경공능장애평분(NDS);재관주24 h시,측정뇌경사구면적(n=10)、뇌조직미관상관단백2(MAP2)표체(n=6)화뇌조직혈장용량、혈관직경화절단장도(n=6).결과 관찰기소유시간점적심솔화평균동맥압(MAP)조간비교차이균무통계학의의(균P＞0.05).재관주24 h후,Ⅰ～Ⅴ조적결혈측뇌경사면적여동측대뇌반구면적적비치(즉뇌경사엄중정도)분별시43%±6%、31%±4%、32%±5%、28%±6%화21%±7%.여Ⅰ조비교,Ⅱ～Ⅴ조적NDS화뇌경사엄중정도균저(균P＜0.05),MAP2표체、혈장용량、혈관직경화절단장도균고,단상술지표재Ⅱ조、Ⅲ조화Ⅵ조지간비교차이균무통계학의의(균P＞0.05).여Ⅰ조、Ⅱ조、Ⅲ조화Ⅳ조비교,Ⅴ조적NDS평분화뇌경사정도균저(균P＜0.05),MAP2표체화혈장용량현저고(균P＜0.05),단시결혈측뇌조직적혈관직경화절단장도재Ⅱ조、Ⅲ조Ⅵ조화Ⅴ조지문차이균무통계학의의(균P＞0.05).결론 재국조성뇌결혈-재관주손상대서,결혈후처리、원격결혈후처리화납락동후처리균구유명현적신경보호작용,표현위뇌경사엄중정도강저화신경공능장애개선.연합응용3충후처리조시가획득증강적신경보호효응.
Objective To assess the effects of ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats.Methods A total of 110 adult SD rats were randomly divided into 5 groups (n =22 each). The focal cerebral ischemia-reperfusion injury was induced by a 90-minute occlusion of right middle cerebral artery (MCA) and a 24-hour reperfusion sequentially. Group 1 was of ischemia-reperfusion control; Group 2 ischemic postconditioning induced by three 30-second cycles of MCA occlusion followed by a 30-second reperfusion; Group 3 remote ischemic postconditioning performed via a transient occlusion of right femoralartery at 5 min before the initiatlon of reperfusion:Group 4 naloxone posteonditioning with naloxone 10 mg/kg intraperitoneaUy injected at the initiation of reperfusion;Group 5 combined ischemic,remote ischernic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2,3 & 4.The neumlogie deftcit scores(NDS)were obtained at 2 h & 24 h post-reperfusion.At 24 h post-reperfusion.the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to asseSS the size ofcerebral infaret(n=10),detect the cerebral expression of microtubule-associated protein2(MAP2)(n=6),measure the plasma volume of cerebral tissues and quantify the diameter and segment artery at 5 min before the initiation of reperfusion; Group 4 naloxone postconditioning with naloxone 10 mg/kg intraperitoneally injected at the initiation of reperfusion; Group 5 combined ischemic, remote ischemic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2, 3 & 4. The neurologic deficit scores ( NDS) were obtained at 2 h & 24 h post-reperfusion. At 24 h post-reperfusion, the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to assess the size of cerebral infarct (n = 10), detect the cerebral expression of microtubule-associated protein2 ( MAP2) (n =6) , measure the plasma volume of cerebral tissues and quantify the diameter and segment length of cerebral microvessel (n = 6 ). Results There were no significant differences in the heart rate (HR) and mean arterial pressure (MAP) among the above five groups at all observed time points (P ＞ 0. 05). At 24 h post-reperfusion, the percentage of ischemic cerebral infarct size was 43% ±6% , 31% ±4% , 32% ±5% , 28% ±6% & 21% ±7% in ipsilateral hemisphere area (i. e. , cerebral infarct severity)in Groups 1-5 respectively. Compared with Group 1, the levels of NDS and cerebral infarct severity significantly decreased at ischemic side in Groups 2-5 ( P ＜ 0. 05 ). And the cerebral expression of MAP2,plasma volume of cerebral tissues, diameter and segment length of cerebral microvessel significantly increased at the ischemic side (all P＜0. 05). However, there were no significant differences in the abovementioned parameters at ischemic side among Groups 2, 3 and 4 (all P ＞0. 05). The parameters of NDS,cerebral infarct severity, cerebral expression of MAP2 and plasma volume of cerebral tissues in the ischemic side significantly increased in Group 5 compared with Groups 1,2,3 and 4 (all P ＜ 0. 05). The diameter and segment length of cerebral microvessel at ischemic side were not different among Groups 2,3,4 and 5 (all P＞0. 05). Conclusion In focal cerebral ischemia-reperfusion rats, ischemic, remote ischemic and naloxone postconditioning may produce significant neuroprotective effects of reduced cerebral infarct severity and improved neurologic dysfunctions. A combination of three postconditioning approaches enhances the above neuroprotective effects.