【摘要】：目的：近年來研究發(fā)現(xiàn)，缺血后處理（Ischemia postconditioning,IP）可以通過激活多種內(nèi)源性途徑對腦缺血發(fā)揮神經(jīng)保護(hù)作用,減少大鼠腦缺血/再灌注（Ischemia/Reperfusion,I/R）損傷。而快速和延遲性遠(yuǎn)程缺血后處理（Remote ischemic postconditioning, RIP）的研究甚少。本課題研究目的是通過線栓法制備穩(wěn)定的大鼠大腦中動(dòng)脈阻塞（Middle cerebralartery occlusion, MCAO）模型，探討快速和延遲性遠(yuǎn)程缺血后處理對大鼠局部腦缺血保護(hù)作用。方法：首先，建立穩(wěn)定的大鼠大腦中動(dòng)脈阻塞(MCAO）線栓模型，將32只健康雄性大鼠(Sprague Dawlay/SD，280-300g)隨機(jī)分為4組:⑴假手術(shù)組（Sham,n=8）：大鼠行MCAO模型手術(shù)，離斷頸外動(dòng)脈后進(jìn)栓，，并且立即拔除線栓，再灌注48小時(shí);(2)照組（Control,n=8）：大鼠大腦中動(dòng)脈阻塞90分鐘，拔除栓線再灌注48小時(shí);(3)R-RIP組（MCAO模型-快速性遠(yuǎn)程缺血后處理組,n=8）：大鼠大腦中動(dòng)脈阻塞90分鐘,拔除栓線再灌注后即刻給予遠(yuǎn)程缺血訓(xùn)練。(4)D-RIP組（MCAO模型-延遲性遠(yuǎn)程缺血后處理組,n=8）：大鼠大腦中動(dòng)脈阻塞90分鐘,拔除栓線再灌注后6小時(shí)給予遠(yuǎn)程缺血訓(xùn)練。遠(yuǎn)程缺血訓(xùn)練即鈍性分離雙側(cè)股動(dòng)脈，再灌注即刻或再灌注后6小時(shí)，用蛙心夾依次夾閉/放開10分鐘，如此進(jìn)行3個(gè)循環(huán)。分別在大腦中動(dòng)脈閉塞后1小時(shí)、再灌注后12小時(shí)、24小時(shí)及48小時(shí)進(jìn)行神經(jīng)功能評分，再灌注48小時(shí)處死大鼠，腦組織制成蠟塊并用HE染色測定腦梗塞體積。結(jié)果：⑴HE染色腦梗塞體積分析表明，相對于對照組，R-RIP和D-RIP組大鼠腦梗死體積明顯減少，有統(tǒng)計(jì)學(xué)意義（P 0.05）；且R-RIP組較D-RIP組大鼠腦梗死體積也明顯減少，有統(tǒng)計(jì)學(xué)意義（P0.05）。⑵各組大鼠大腦中動(dòng)脈閉塞后1小時(shí)、再灌注后12小時(shí)、24小時(shí)及48小時(shí)進(jìn)行神經(jīng)功能評分結(jié)果顯示，相對于對照組，R-RIP和D-RIP組神經(jīng)功能評分明顯增加，具有統(tǒng)計(jì)學(xué)意義（P0.05）。遠(yuǎn)程缺血后處理組在大鼠大腦中動(dòng)脈閉塞后1小時(shí)、再灌注后12小時(shí)及24小時(shí)D-RIP組較R-RIP組神經(jīng)功能評分有減少趨勢，但無統(tǒng)計(jì)學(xué)差異（P0.05）；而再灌注后48小時(shí)D-RIP較R-RIP組的神經(jīng)功能評分明顯減少，有統(tǒng)計(jì)學(xué)意義（P0.05）。結(jié)論：本實(shí)驗(yàn)研究表明快速和延遲性遠(yuǎn)程缺血后處理均可以減少大鼠腦缺血梗死體積，改善神經(jīng)功能評分，具有腦神經(jīng)保護(hù)作用；且快速性遠(yuǎn)程缺血后處理更明顯減少大鼠腦梗死體積而延遲性遠(yuǎn)程缺血后處理，尤其再灌注后48小時(shí)可以改善神經(jīng)功能評分。
[Abstract]:Objective: in recent years, it has been found that Ischemia postconditioning IP can play a neuroprotective role in cerebral ischemia by activating a variety of endogenous pathways and reduce the injury of cerebral ischemia / reperfusion (I / R) in rats. However, there is little research on rapid and delayed long-distance ischemic (Remote ischemic postconditioning, RIP). The purpose of this study was to establish a stable (Middle cerebralartery occlusion, MCAO) model of middle cerebral artery occlusion (MCAO) in rats by the method of thread occlusion, and to investigate the protective effect of rapid and delayed remote ischemic postprocessing on local cerebral ischemia in rats. Methods: first of all, a stable middle cerebral artery occlusion model of (MCAO) was established in rats. Thirty-two healthy male rats (Sprague Dawlay / SD 280-300g) were randomly divided into 4 groups: sham 1 sham-operated group (Shamma nunnion 8): rats underwent MCAO model operation, and were removed from the external carotid artery. The middle cerebral artery (MCA) was occluded for 90 minutes, and the thrombus was removed for 48 hours. (3) R-RIP group (MCAO model-rapid remote ischemic postprocessing group): middle cerebral artery occlusion in rats for 90 minutes. (4) D-RIP group (MCAO model-delayed remote ischemic post-treatment group): middle cerebral artery occlusion was performed for 90 minutes in rats, and long distance ischemia training was given 6 hours after the removal of thrombus thread after reperfusion. The bilateral femoral arteries were obtuse separated by remote ischemic training. Immediately after reperfusion or 6 hours after reperfusion, the frog's heart clamp was used to clamp / release for 10 minutes in turn, and three circulations were carried out in this way. The neurological function was assessed at 1 hour after middle cerebral artery occlusion, 24 hours after reperfusion and 48 hours after reperfusion. The rats were killed at 48 hours after reperfusion, and the cerebral infarction volume was measured by HE staining. Results compared with the control group, the infarct volume of the rats in the R-RIP and D-RIP groups was significantly decreased (P 0.05), and the infarct volume in the R-RIP group was significantly lower than that in the D-RIP group (P 0.05), and the cerebral infarction volume in the R-RIP group was significantly lower than that in the D-RIP group (P < 0.05). There was statistical significance (P0.05). 2 the neurological function scores were significantly increased in the middle cerebral artery occlusion group 1 hour after reperfusion 12 hours after reperfusion 24 hours and 48 hours after reperfusion compared with the control group R-RIP and D-RIP group. There was statistical significance (P0.05). Compared with R-RIP group, the scores of nerve function in the remote ischemic post-treatment group decreased at 1 hour after middle cerebral artery occlusion, 12 hours and 24 hours after reperfusion, but there was no statistical difference (P0.05). 48 hours after reperfusion, the neurological function score of D-RIP group was significantly lower than that of R-RIP group (P0.05). Conclusion: this experimental study shows that both rapid and delayed remote ischemic postprocessing can reduce the volume of cerebral ischemia infarction, improve the neurological function score, and have neuroprotective effect. Rapid remote ischemic postprocessing significantly reduced the volume of cerebral infarction in rats, but delayed remote ischemic postprocessing, especially 48 hours after reperfusion, which could improve the neurological function score.
【學(xué)位授予單位】：桂林醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R743.32


本文編號(hào)：2181147