首页> 中文期刊> 《山东医药》 >异氟醚后处理对缺血缺氧性脑损伤新生大鼠的长期脑保护作用及机制探讨

异氟醚后处理对缺血缺氧性脑损伤新生大鼠的长期脑保护作用及机制探讨

         

摘要

Objective To investigate long-term brain protective effect and mechanism of isoflurane postconditioning on hypoxic-ischemic brain injury(HIBI) in neonatal rats.Methods 105 Sprague-Dawley(SD)neonatal rats were randomly divided into sham surgery group , model group , isoflurane group , atractyloside group , atractyloside with isoflurane group , cyclosporine group and cyclosporine with isoflurane group .Each group had left common carotid arterial ligation ( sham group threading without ligation ) followed by 8% oxygen and 92% nitrogen mixed gas .After model was established ( or sham surgery), injected drug in lateral ventricle: two atractyloside group were injected atractyloside , two cyclosporine group were injected cyclosporine A , other groups were injected saline .1.5%isoflurane were inhaled in isoflurane process-ing group for 30 min.Evaluating cognitive function by Morris water maze test (MWM) in the 30th to 35th days.Neuronal density ration in thalamic ventral posteromedial nucleus and hippocampal CA 3 region of left to right cerebral hemisphere were calculated after the MWM .Results Compared with sham surgery group , the average escape latency time and swim-ming routes was longer(P<0.05), while the number of crossing platform, the percentage of platform quadrant time and platform quadrant routes were reduced in model group , two atractyloside group , and there was no significant difference in isoflucane group and two cyclosporine group , while neuronal density ration were reduced(P<0.05)in other groups.Com-pared with model group, the average escape latency time and swimming routes were shorter (P<0.05), while the number of crossing platform , the percentage of platform quadrant time and platform quadrant routes and neuronal density ration were increased(P<0.05)in isoflurane group and two cyclosporine group .While there was no significant difference in above in-dex in two atractyloside group(P>0.05).Compared with isoflurane group, the average escape latency time and swimming routes were longer ( P<0 .05 ) , while the number of crossing platform , the percentage of platform quadrant time platform quadrant routes and neuronal density ration were reduced (P<0.05) in two atractyloside group(P<0.05),and there was no significant difference in two cyclosporine group (P>0.05).Conclusion Isoflurane postconditioning has long-term pro-tective effect on reducing HIBI neonatal rats , and the mechanism may be by inhibiting the openness of mPTP .%目的:探讨异氟醚后处理对缺血缺氧性脑损伤( HIBI)新生大鼠的长期脑保护作用及机制。方法将105只新生SD大鼠随机分为假手术组、模型组、异氟醚、苍术苷组、苍术苷+异氟醚组、环孢素组、环孢素+异氟醚组,每组各15只。除假手术组外其余各组均制作HIBI模型。模型建立后侧脑室注射药物:苍术苷组、苍术苷+异氟醚组注射线粒体通道转换孔( mPTP)特异性开放剂苍术苷;环孢素组、环孢素+异氟醚组注射mPTP特异性抑制剂环孢素A;其余组注射生理盐水;在此基础上各异氟醚组予异氟醚后处理:吸入含1.5%异氟醚的湿化混合气体30 min,2 L/min。干预后30~35 d行Morris水迷宫试验,评估大鼠学习记忆功能;计数丘脑腹后内侧核和海马CA3区左、右侧正常神经元密度比值。结果与假手术组比较,模型组及苍术苷组、苍术苷+异氟醚组平均逃逸潜伏期延长,穿平台次数、平台象限时间百分比、平台象限路程百分比降低(P均<0.05);各组丘脑腹后内侧核及海马CA3区左、右侧神经元密度的比值均降低( P<0.05)。与模型组比较,异氟醚组、环孢素组、环孢素+异氟醚组平均逃逸潜伏期缩短,穿平台次数、平台象限时间百分比、平台象限路程百分比、丘脑腹后内侧核及海马CA3区左、右侧神经元密度比值升高( P均<0.05)。与异氟醚组比较,苍术苷组、苍术苷+异氟醚组平均逃逸潜伏期延长次数、平台象限时间百分比、平台象限路程百分比、丘脑腹后内侧核及海马CA3区左、右侧神经元密度比降低( P均<0.05)。结论异氟醚后处理对HIBI新生大鼠具有长期脑保护作用,其机制可能为抑制mPTP开放。

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