13-甲基十四烷酸对大鼠脑缺血后脑水肿的影响
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摘要
目的研究13-甲基十四烷酸(13-methyltetradecanoic acid, 13-MTD)对脑缺血后脑水肿的影响及其机制。方法线栓法制备大鼠大脑中动脉闭塞模型,于插入栓线前30 min分别尾静脉注射13-MTD 40、80、120 mg·kg~(-1)(M40、M80、M120),阴性对照组给予等体积脂质体。于缺血6、12、24 h,以Longa神经功能缺失评分观察神经功能缺失症状;TTC染色观察脑梗死体积大小;AutoCAD图像分析软件计算脑水肿程度;脑干湿重测定脑含水量;伊文思蓝(EB)检测血脑屏障通透性;RT-PCR检测损伤侧脑组织AQP4 mRNA表达;免疫组化法检测损伤侧脑组织AQP4蛋白表达。结果 13-MTD可明显改善脑缺血大鼠神经功能缺失症状,使脑梗死体积明显缩小,使脑含水量和脑水肿程度明显减轻,EB渗出减少,明显改善缺血侧脑组织AQP4表达。结论 13-MTD能通过调控AQP4表达,减轻大鼠脑缺血后脑水肿。
Aim To investigate the effect of 13-methyltetradecanoic acid(13-MTD) on brain edema after cerebral ischemia in rats and its mechanism. Methods The model of middle cerebral artery occlusion(MCAO) was prepared by suture embolization method. Thirty minutes prior to the insertion of the embolus, tail vein injection of 13-MTD 40, 80, 120 mg·kg~(-1)(M40, M80, M120) was respectively performed. The negative control group was given an equal volume of liposomes. 6, 12 and 24 h after ischemia, neurological deficits were observed with Longa neurological deficit scores; brain infarct volume was observed with TTC staining; brain edema was calculated with AutoCAD image analysis software; brain water content was measured with brain dry weight; the blood-brain barrier(BBB) permeability was measured by Evans blue(EB). AQP4 mRNA expression in the injured brain tissue was detected by RT-PCR. The expression of AQP4 protein in the injured brain tissues was detected by immunohistochemistry. Results 13-MTD could significantly improve the symptoms of neurological deficits in rats with cerebral ischemia, reduce the volume of cerebral infarction, decrease brain water content and cerebral edema, and down-regulate EB leakage, and up-regulate the expression of AQP4 in the ischemic brain tissues. Conclusion 13-MTD can reduce brain edema after cerebral ischemia in rats by regulating AQP4 expression.
Aim To investigate the effect of 13-methyltetradecanoic acid(13-MTD) on brain edema after cerebral ischemia in rats and its mechanism. Methods The model of middle cerebral artery occlusion(MCAO) was prepared by suture embolization method. Thirty minutes prior to the insertion of the embolus, tail vein injection of 13-MTD 40, 80, 120 mg·kg~(-1)(M40, M80, M120) was respectively performed. The negative control group was given an equal volume of liposomes. 6, 12 and 24 h after ischemia, neurological deficits were observed with Longa neurological deficit scores; brain infarct volume was observed with TTC staining; brain edema was calculated with AutoCAD image analysis software; brain water content was measured with brain dry weight; the blood-brain barrier(BBB) permeability was measured by Evans blue(EB). AQP4 mRNA expression in the injured brain tissue was detected by RT-PCR. The expression of AQP4 protein in the injured brain tissues was detected by immunohistochemistry. Results 13-MTD could significantly improve the symptoms of neurological deficits in rats with cerebral ischemia, reduce the volume of cerebral infarction, decrease brain water content and cerebral edema, and down-regulate EB leakage, and up-regulate the expression of AQP4 in the ischemic brain tissues. Conclusion 13-MTD can reduce brain edema after cerebral ischemia in rats by regulating AQP4 expression.
引文
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[7] Xu H M, Wei E Q, Zhang S H, et al.Macrophotographic measurement of brain surface area for evaluating brain edema after focal cerebral ischemia in mice[J]. J Zhejiang Univ (Med Sci), 2003,(6): 37-41.
[8] Pirici I, Balsanu T A, Bogdan C, et al.Inhibition of aquaporin-4 improves the outcome of ischaemic stroke and modulates brain paravascular drainage pathways[J]. Int J Mol Sci, 2018, 19(1):46.
[9] Hosomi N, Lucero J, Heo J H, et al.Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion[J]. Stroke, 2001, 32(6): 1341-8.
[10] Truong D T, Venna V R, McCullough L D, et al.Deficits in auditory, cognitive, and motor processing following reversible middle cerebral artery occlusion in mice[J]. Exp Neurol, 2012, 238(2): 114-21.
[11] Zador Z, Stiver S, Wang V, et al. Role of aquaporin-4 in cerebral edema and stroke[J]. Handb Exp Pharmacol, 2009,2009(190): 159-70.
[12] 符师宁, 胡丹辰, 闫军浩.水通道蛋白4在脑缺血后脑水肿中的作用[J]. 生理科学进展,2016,47(5): 361-4.
[12] Fu S N,Hu D C, Yang J H. The role of aquaporin 4 in cerebral edema after cerebral ischemia[J]. Prog Physiol Sci, 2016,47(5): 361-4.
[13] Cai L, Lei C, Li R, et al. Aquaporin-4 blockage by siRNA protects rat articular chondrocytes from IL-1β-induced apoptosis by inhibiting p38 MAPK signal pathway[J]. Ann Clin Lab Sci, 2017,47(5):563-71.
[14] Lin, Yin X, Cai Q, et al.13-Methyltetradecanoic acid induces mitochondrial-mediated apoptosis in human bladder cancer cells[J]. Urol Oncol, 2012,30(3):339-45.
[2] 许淑红, 康辰, 陈美灵,等.大鼠脑缺血/再灌注后早期AQP4的动态表达及其与脑水肿关系的研究[J]. 中国药理学通报, 2016, 32(10): 1433-41.
[2] Xu S H,Kang C,Chen M L, et al.Dynamic expression of AQP4 in early stage of ischemia/reperfusion rats and cerebral edema[J]. Chin Pharmacol Bull, 2016,32(10):1433-41.
[3] Faung S T, Chiu L, Wang C T. Platelet lysis and functional perturbation by 13-methyl myristate. The major fatty acid in Flavobacterium ranacida[J]. Thromb Res, 1996, 81(1): 91-100.
[4] 宋百颖,赖文芳,苏燕青,等.红景天苷通过抑制补体C3的表达对MCAO大鼠缺血侧NeuN、Egr4影响的研究[J]. 中国药理学通报,2017,33(11):1579-84.
[4] Song B Y,Lai W F,Su Y Q, et al. Effects of salidroside on expression of NeuN and Egr4 in ischemic side of MCAO rats by inhibiting expression of C3[J]. Chin Pharmacol Bull, 2017,33(11):1579-84.
[5] 文静,王建,陈念,等.安息香对永久性大脑中动脉栓塞大鼠模型的保护作用及其机制研究[J]. 中国药理学通报, 2016,33(12):1683-7.
[5] Wen J, Wang J,Chen N, et al. Study of protective effects and mechanism of benzoinum against permanent focal cerebral ischemia injury in rats[J]. Chin Pharmacol Bull, 2016,33(12):1683-7.
[6] Longa E Z, Weinstein P R, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1):84-91.
[7] 徐慧敏, 魏尔清, 张世红,等.脑表面大体摄影评价小鼠局灶性脑缺血后脑水肿变化[J].浙江大学学报(医学版), 2003,32(6): 37-41.
[7] Xu H M, Wei E Q, Zhang S H, et al.Macrophotographic measurement of brain surface area for evaluating brain edema after focal cerebral ischemia in mice[J]. J Zhejiang Univ (Med Sci), 2003,(6): 37-41.
[8] Pirici I, Balsanu T A, Bogdan C, et al.Inhibition of aquaporin-4 improves the outcome of ischaemic stroke and modulates brain paravascular drainage pathways[J]. Int J Mol Sci, 2018, 19(1):46.
[9] Hosomi N, Lucero J, Heo J H, et al.Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion[J]. Stroke, 2001, 32(6): 1341-8.
[10] Truong D T, Venna V R, McCullough L D, et al.Deficits in auditory, cognitive, and motor processing following reversible middle cerebral artery occlusion in mice[J]. Exp Neurol, 2012, 238(2): 114-21.
[11] Zador Z, Stiver S, Wang V, et al. Role of aquaporin-4 in cerebral edema and stroke[J]. Handb Exp Pharmacol, 2009,2009(190): 159-70.
[12] 符师宁, 胡丹辰, 闫军浩.水通道蛋白4在脑缺血后脑水肿中的作用[J]. 生理科学进展,2016,47(5): 361-4.
[12] Fu S N,Hu D C, Yang J H. The role of aquaporin 4 in cerebral edema after cerebral ischemia[J]. Prog Physiol Sci, 2016,47(5): 361-4.
[13] Cai L, Lei C, Li R, et al. Aquaporin-4 blockage by siRNA protects rat articular chondrocytes from IL-1β-induced apoptosis by inhibiting p38 MAPK signal pathway[J]. Ann Clin Lab Sci, 2017,47(5):563-71.
[14] Lin, Yin X, Cai Q, et al.13-Methyltetradecanoic acid induces mitochondrial-mediated apoptosis in human bladder cancer cells[J]. Urol Oncol, 2012,30(3):339-45.
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