Protective effects of nicorandil against cerebral injury in a swine cardiac arrest model.
Protective effects of nicorandil against cerebral injury in a swine cardiac arrest model.
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尼可地尔对猪心脏骤停模型脑损伤的保护作用
DOI：
10.3892/etm.2018.6136
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发表时间：
2018-07
影响因子：
2.7
通讯作者：
Shang D
中科院分区：
文献类型：
--
作者：
Zhu F;Zhong X;Zhou Y;Hou Z;Hu H;Liang L;Chen J;Chen Q;Ji X;Shang D
本研究在猪心脏骤停模型中研究了尼可地尔对心肺复苏（CPR）后脑损伤的影响。在诱导室颤4 min后对猪进行CPR。存活动物随机分为3组：尼可地尔组（n=8）、对照组（n=8）和假手术组（n=4）。假手术组采用相同的手术方法模拟心脏骤停，但不诱导室颤。当检测到最早可观察到的自主循环恢复（ROSC）时，尼可地尔组和对照组分别接受尼可地尔和生理盐水注射。在基线和ROSC后5 min、0.5、3和6 h收集猪血清。采用酶联免疫吸附法（ELISA）检测血清神经元特异性烯醇化酶（NSE）、S100β、肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）水平。在ROSC后6小时，对动物实施安乐死，收集脑组织样品并使用光学和电子显微镜进行评估。采用免疫印迹法检测脑组织水通道蛋白4（AQP-4）的表达。采用硫代巴比妥酸比色法和硫代苯甲酸比色法分别测定脑组织丙二醛（MDA）和谷胱甘肽（GSH）含量。尼可地尔组和对照组心肺复苏后血清NSE和S100β水平均较复苏前显著升高（P<0.05）。尼可地尔组NSE和S100β水平显著低于对照组（P<0.05）。病理学检查和电子显微镜检查表明尼可地尔可减轻脑组织损伤。尼可地尔组TNF-α和IL-6水平较对照组显著降低（P<0.05）。尼可地尔组ROSC后6 h脑组织AQP-4表达明显低于对照组（P<0.05）。尼可地尔组猪脑组织中MDA和GSH水平分别较对照组降低和升高（P<0.05）。本研究的结果表明，尼可地尔通过减少ROSC后的氧化损伤、炎症反应和脑水肿，对心脏骤停后的脑损伤发挥保护作用。
The present study investigated the effects of nicorandil on cerebral injury following cardiopulmonary resuscitation (CPR) in a swine model of cardiac arrest. CPR was performed on swine following 4 min induced ventricular fibrillation. Surviving animals were randomly divided into 3 groups: A nicorandil group (n=8), a control group (n=8) and a sham group (n=4). The sham group underwent the same surgical procedure to imitate cardiac arrest, but ventricular fibrillation was not induced. When the earliest observable return of spontaneous circulation (ROSC) was detected, the nicorandil and control groups received injections of nicorandil and saline, respectively. Swine serum was collected at baseline and 5 min, 0.5, 3 and 6 h following ROSC. Serum levels of neuron-specific enolase (NSE), S100β, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured using ELISA. Animals were euthanized and brain tissue samples were collected and assessed using light and electron microscopy 6 h following ROSC. The expression of aquaporin-4 (AQP-4) in the brain tissue was measured using western blotting. Malondialdehyde (MDA) and glutathione (GSH) levels in the brain tissue were determined using thiobarbituric acid and thiobenzoic acid colorimetric methods, respectively. Serum NSE and S100β were significantly higher in the nicorandil and control groups following CPR, compared with baseline (P<0.05). Additionally, NSE and S100β levels were significantly lower in the nicorandil group compared with the control (P<0.05). Pathological examinations and electron microscopy indicated that nicorandil reduced brain tissue damage. TNF-α and IL-6 levels were significantly decreased in the nicorandil group compared with the control group (P<0.05). Furthermore, AQP-4 expression in brain tissue 6 h following ROSC was significantly lower in the nicorandil group compared with the control group (P<0.05). MDA and GSH levels in swine brain tissue decreased and increased, respectively, in the nicorandil group compared with the control group (P<0.05). The results of the present study demonstrate that nicorandil exerts a protective effect against brain injury following cardiac arrest by reducing oxidative damage, inflammatory responses and brain edema post-ROSC.
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影响因子：
8.3
作者：
Kleffner, Ilka;Bungeroth, May;Kuhlenbaeumer, Gregor
通讯作者：
Kuhlenbaeumer, Gregor
影响因子：
9.9
作者：
KRUMHOLZ, A;STERN, BJ;WEISS, HD
通讯作者：
WEISS, HD
影响因子：
2.9
作者：
Dunn-Meynell, AA;Rawson, NE;Levin, BE
通讯作者：
Levin, BE
DOI：
10.1073/pnas.0902725106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Ho, Joseph D.;Yeh, Ronald;Stroud, Robert M.
通讯作者：
Stroud, Robert M.
影响因子：
2.9
作者：
MARANGOS, PJ;SCHMECHEL, DE;GOODWIN, FK
通讯作者：
GOODWIN, FK