Highly selective non-opioid kappa opioid receptor (KOR) agonist salvinorin A protects against forebrain ischemia-induced brain injury in rats
Highly selective non-opioid kappa opioid receptor (KOR) agonist salvinorin A protects against forebrain ischemia-induced brain injury in rats
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高选择性非阿片 kappa 阿片受体 (KOR) 激动剂 salvinorin A 可预防大鼠前脑缺血引起的脑损伤
DOI：
10.1016/j.brainres.2016.02.024
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发表时间：
2016-04
期刊：
影响因子：
2.9
通讯作者：
Wang, Zhenhong
中科院分区：
文献类型：
--
作者：
Xin, Jihua;Zhang, Yan;He, Zhenzhou;Wang, Zhenhong
目的采用大鼠前脑缺血再灌流模型，观察丹参甲素(SA)对脑缺血再灌流(I/R)后脑损伤和神经功能的影响，并进一步探讨SA抑制kappa阿片受体(KOR)对前脑海马区、皮质和纹状体水通道蛋白4(AQP4)表达的影响。大鼠随机接受二甲基亚砜(DMSO)、SA(1微克/100毫克体重)或SA(缺血发作)加SA拮抗剂NOR-BIN(0.2微克/100毫克体重)。测定大鼠脑含水量。计数大鼠海马CA1区、皮质和纹状体的神经元凋亡数。用免疫印迹和免疫组织化学方法检测脑缺血24 h后CA1区、皮质和纹状体中AQP4的表达。分别于缺血后第1、2、5天进行神经运动测试。于缺血后第5天进行水迷宫实验。结果SA可明显减轻I/R引起的脑组织含水量的增加。免疫印迹分析和免疫组织化学结果进一步表明，SA能有效抑制缺血24小时后脑缺血再灌流引起的海马区、皮质区和纹状体AQP4表达上调。与DMSO相比，SA还显著降低了这些区域的死亡和凋亡神经元的百分比。此外，SA还部分逆转了I/R所致的大鼠运动功能和认知功能的下降。结论SA对大鼠脑I/R损伤具有保护作用，其机制可能是通过减少脑水肿形成和抑制神经元死亡，促进大鼠脑I/R后神经功能恢复。
ObjectiveTo investigate the effect of salvinorin A (SA) on brain injury and neurologic function post-brain ischemia/reperfusion (I/R) using a rat forebrain ischemia model and further explore the effect of kappa opioid receptor (KOR) inhibition by SA on aquaporin-4 (AQP4) expression in the hippocampus, cortex and striatum in the forebrain.MethodsA forebrain ischemia model was established by colligating the bilateral common carotid arteries of SD rats for 10 min. The rats were randomized to receive dimethyl sulfoxide (DMSO), SA (1 µg/100 g body weight) or SA (onset of ischemia) plus SA antagonist nor-BIN (0.2 mg/100 g body weight. Rat brain water content was measured. Apoptotic neurons in the hippocampal CA1 region, cortex and striatum were enumerated. AQP4 in CA1, the cortex and the striatum were determined by immunoblotting assays and immunohistochemistry at 24 h post-ischemia. Neuromotor tests were performed on day 1, 2 and 5 post-ischemia. Water maze test was carried out on the 5th post-ischemia day.ResultsSA significantly attenuated I/R-induced increase in brain water content. Our immunoblotting assays and immunohistochemistry further revealed that SA effectively lessened I/R-induced upregulation of AQP4 expression in the hippocampus, cortex and striatum 24 h post-ischemia. SA also significantly reduced the percentage of dead and apoptotic neurons in these regions compared to DMSO. Moreover, SA partially reversed I/R-induced decline in rat motor function and cognition. The neuroprotective effects of SA were partially abolished by nor-BIN.ConclusionSA protects against I/R-induced brain injury by attenuating brain edema formation and inhibiting neuronal death and improves neurologic recovery of rats post-I/R.
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DOI：
--
发表时间：
1997-07
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
C. Guéniau;C. Oberlander
通讯作者：
C. Guéniau;C. Oberlander
DOI：
--
发表时间：
2014
期刊：
Translational perioperative and pain medicine
影响因子：
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作者：
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通讯作者：
Chunhua Chen;Chunhua Xi;Sugita Megumi;Liu Renyu
影响因子：
4.2
作者：
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通讯作者：
Chan, Pak H.
影响因子：
4.2
作者：
Ribeiro, Marlise de Castro;Hirt, Lorenz;Badaut, Jerome
通讯作者：
Badaut, Jerome
影响因子：
7.2
作者：
Lee, Kyungjin;Jo, In-Young;Bu, Youngmin
通讯作者：
Bu, Youngmin