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托吡酯对硝酸甘油致大鼠偏头痛模型血浆和脑组织中水通道蛋白1表达的影响

Effect of Topiramate on Expression of Aquaporin 1 in Blood Plasma and Cerebral Tissue from Rat Model of Migraine with Nitroglycerin

【作者】 杨志亮

【导师】 孙桂莲;

【作者基本信息】 中国医科大学 , 儿科学, 2010, 硕士

【摘要】 目的研究硝酸甘油致大鼠偏头痛模型血浆和脑组织中水通道蛋白1(AQP1)的表达,并研究托吡酯(TPM)对此表达的影响。方法SD大鼠50只,随机分成3组,对照组10只,模型组25只,治疗组15只。对照组皮下注射生理盐水,4小时后灌胃生理盐水2ml/kg;其余大鼠均皮下注射硝酸甘油注射剂10mg/kg,建立实验性偏头痛模型,造模成功后随机分为两组,模型组每日相同时间皮下注射硝酸甘油注射剂,4小时后灌胃生理盐水,共7d;治疗组每日相同时间皮下注射硝酸甘油注射剂,4小时后灌胃TPM 7d。各组末次处理4h后,将动物处死,取血和脑组织备用。实验结束时统计每组大鼠的存活数,应用酶联免疫吸附测定(ELISA)检测血浆中的AQP1浓度,脑组织切片进行HE染色及AQP1免疫组化染色检测,免疫组化染色切片经NIS-ELEMENTS F系统采集图像,MetaMorph offline软件系统测量平均积分光密度(IOD)值。结果1、三组存活数:对照组存活10只,模型组25只存活10只,治疗组15只存活10只。模型组与治疗组的存活数比较有统计学差异(p<0.05),2、ELISA检测结果:对照组AQP1的浓度明显低于模型组和治疗组(p<0.05),模型组与治疗组的AQP1浓度无明显差异(p>0.05),3、HE染色:三组未见异常病变,也未见明显差异,4、AQP1免疫组化检测:阳性细胞为在细胞膜上和细胞浆中有棕黄色表达,通过测量平均IOD值比较:模型组和治疗组脑组织的AQP1的免疫组化IOD值高于对照组,有统计学差异(p<0.05),模型组脑组织中的AQP1平均IOD值稍高于治疗组,但统计学上无明显差异(p>0.05)。结论AQP1在硝酸甘油致偏头痛大鼠模型血浆和脑组织中的表达增加,提示其在偏头痛的发病机制中可能发挥着重要的作用,而TPM是否通过影响AQP1的表达来治疗偏头痛不能确定。

【Abstract】 ObjectiveTo investigate the expression of aquaporin 1 (AQP1) in blood plasma and cerebral tissue from rat model of migraine with nitroglycerin and effect of topiramate (TPM) on the expression.Method50 SD rats were selected and randomly divided into 3 groups:control group:10 rats, modelset group:25 rats, treatment group:15rats. From the first day, rats of control group were given Normal Saline(2ml/kg) by hypodermic injection and given Normal Saline(2ml/kg) by lavage after 4 hour (to eliminate the effect to rats of hypodermic injection and lavage) from 1st day to 7th day; rats of modelset group were given nitroglycerin injection (10mg/kg) by hypodermic injection and were given Normal saline(2ml/kg) by lavage after 4 hour from 1st day to 7th day; rats of treatment group were given nitroglycerin injection (10mg/kg) by hypodermic injection and then were given topiramate (50mg/kg) by lavage after 4 hour from 1st day to 7th day. At 7th day, rats of each group were narcotized by 10%chloral hydrate at 4 hours after the last respective operation,then get blood and cerebral tissue, to measure concentration in blood and to observe histological change by light microscope and to measure values of average Integrated Optical Density (IOD) for AQP1 by immunohistochemical stains.Result1、survival of the rats:10 rats of control group survived,10 rats in 25 of modelset group survived,10 rats in 15 of treatment group survived, the difference of survival between modelset group and treatment group has statistical difference (P<0.05).2、results of AQP1 from ELISA:modelset group and treatment group show no statistical difference (P>0.05), control group and modelset group or treatment group both show statistical difference (P<0.05).3、results from HE stains:there were no abnormal changes obviously, and no obvious difference among groups.4、expression of AQP1 by immunohistochemical stains in cerebral tissue:average IOD value of control group show lower than that of modelset group or treatment group and both show statistical difference (P<0.05), modelset group show slightly stronger than treatment group,but show no statistical difference (P>0.05).ConclusionIn the attack of rat model of migraine with nitroglycerin, AQP1 may partake in the attack of migraine, but it cannot conclude that TPM maybe has effect on the expression of AQP1 as to be one of mechanisms of treatment for topiramate to migraine.

【关键词】 水通道蛋白1偏头痛托吡酯大鼠硝酸甘油
【Key words】 Aquaporin 1migrainetopiramateratnitroglycerin injection
  • 【分类号】R965;R747.2
  • 【被引频次】1
  • 【下载频次】126
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