人工麝香对大鼠急性脑缺血再灌损伤和脑出血的实验治疗
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摘要
采用大鼠局灶性脑缺血再灌注和蛛网膜下腔出血的动物模型,评价人工麝香对缺血性脑卒中和出血性脑卒中的治疗作用,为人工麝香的临床应用提供研究基础。所有动物实验都遵循北京协和医学院动物伦理委员会的规定。结果显示,大脑中动脉阻断或蛛网膜下腔出血5 min后灌胃给予人工麝香对急性缺血性和出血性脑卒中均具有明显的保护作用。在10～200 mg·kg~(-1)剂量范围内,对模型大鼠的死亡率、神经行为学和脑梗死体积具有一定的量效关系。其中在缺血性脑卒中,人工麝香的有效剂量为10 mg·kg~(-1);在出血性脑卒中,其有效剂量为200 mg·kg~(-1)。上述研究结果提示人工麝香在治疗缺血性脑卒中和出血性脑卒中时存在一定差别,临床使用中要给予区别。
The rat models of focal cerebral ischemic reperfusion and subarachnoid hemorrhage were used to evaluate the therapeutic effects of artificial musk to provide support for its clinical application. All animal experiments were performed following the regulations of the Animal Ethics Committee of Peking Union Medical College. The results showed that oral administration of artificial musk had significant protective effects on acute ischemic and hemorrhagic stroke. In the dose range of 10-200 mg · kg~(-1), the mortality, neurobehavioral and cerebral infarction volume of rats in model group indicated a clear dose dependent relationship. The effective dose of artificial musk is 10 mg·kg~(-1) in ischemic stroke and 200 mg·kg~(-1) in hemorrhagic stroke. These findings suggest that the treatments of artificial musk in ischemic stroke and in hemorrhagic stroke are different, and such differences should be noted for its clinical use.
The rat models of focal cerebral ischemic reperfusion and subarachnoid hemorrhage were used to evaluate the therapeutic effects of artificial musk to provide support for its clinical application. All animal experiments were performed following the regulations of the Animal Ethics Committee of Peking Union Medical College. The results showed that oral administration of artificial musk had significant protective effects on acute ischemic and hemorrhagic stroke. In the dose range of 10-200 mg · kg~(-1), the mortality, neurobehavioral and cerebral infarction volume of rats in model group indicated a clear dose dependent relationship. The effective dose of artificial musk is 10 mg·kg~(-1) in ischemic stroke and 200 mg·kg~(-1) in hemorrhagic stroke. These findings suggest that the treatments of artificial musk in ischemic stroke and in hemorrhagic stroke are different, and such differences should be noted for its clinical use.
引文
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[14] Zhu X, Li H, Yu B, et al. Effect of artificial musk on myocardial ischemia in animals[J]. Chin Pharmacol Bull(中国药理学通报),2009, 25:951-954.
[15] Dong SF, Lou LM, Zhang SF, et al. Protective effect of AnGong-Niu-Huang-Wan(containing natural or artificial moschus)on experimental cerebral ischemia in rats[J]. World Sci Technol Mod Trad Chin Med Mater Med(世界科学技术一中医药现代化),2013, 15:85-90.
[2] Jiang Y, Li X, Hu N, et al. Epidemiologic characteristics of cerebrovascular disease mortality in China,2004-2005[J]. Chin J Prey Med(中华预防医学杂志),2010, 44:293-297.
[3] Yang Q, Meng X, Xia L, et al. Conservation status and causes of decline of musk deer(Moschus spp.)in China[J]. Biol Conserv,2003, 109:333-342.
[4] Yu DQ. Research on artificial musk[J]. Bull Med Res(医药研究通讯),2000, 29:16-17.
[5] Xu Q, Liu Y, Shen Q, et al. Effect of artificial musk on the expression of MMP-9 mRNA in rats after focal cerebral ischemiareperfusion[J]. J Trop Med(热带医学杂志),2011,11:875-878.
[6] Longa E,Weinstein P, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke,1989, 20:84-91.
[7] Veelken J, Laing R, Jakubowski J. The Sheffield model of subarachnoid hemorrhage in rats[J]. Stroke, 1995,26:1279-1283.
[8] Bederson JB, Pitts LH, Tsuji M, et al. Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination[J]. Stroke, 1986, 17:472-476.
[9] Belayev L, Alonso OF, Busto R, et al. Middle cerebral artery occlusion in the rat by intraluminal suture:neurological and pathological evaluation of an improved model[J]. Stroke, 1996,27:1616-1622.
[10] Zhu XY, Wang WJ, Xu GF, et al. The pharmacological activities of muskⅡ. The anti-inflammatory activity of the active components of musk[J]. Acta Pharm Sin(药学学报),1988, 23:406-410.
[11] Kadota S, Orito T, Kikuchi T, et al. Musclide-A1,-A2, and-B,cardiotonic potentiating principles from musk[J]. Tetrahedron Lett, 1991,32:1733-1736.
[12] Li H, Li J, Chen T, et al. Efects of synthetic musk on clottingtime and platelet aggregation rate in acute blood-stasis model rats[J]. Chin J Clin Pharmacol Ther(中国临床药理学与治疗学),2009, 14:1004-1007.
[13] Li H, Zhu X, Wu Q. Effects of artificial musk on hyperlipemia in rats[J]. Chin J Clin Pharmacol Ther(中国临床药理学与治疗学),2010, 15:1008-1011.
[14] Zhu X, Li H, Yu B, et al. Effect of artificial musk on myocardial ischemia in animals[J]. Chin Pharmacol Bull(中国药理学通报),2009, 25:951-954.
[15] Dong SF, Lou LM, Zhang SF, et al. Protective effect of AnGong-Niu-Huang-Wan(containing natural or artificial moschus)on experimental cerebral ischemia in rats[J]. World Sci Technol Mod Trad Chin Med Mater Med(世界科学技术一中医药现代化),2013, 15:85-90.