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目的:探讨龙胆碱对反复高热惊厥大鼠的抗惊厥作用机制。方法:60只SD大鼠随机分为健康对照组、模型组、龙胆碱高、低剂量组,各15只。除健康对照组外,其余大鼠均按照文献方法制作高热惊厥大鼠模型。大鼠隔日诱导惊厥1次,共诱导10次,20 d。龙胆碱高、低剂量组每次惊厥后立即分别给予龙胆碱生理盐水溶液200,50 mg.kg-1,ip,模型组和健康对照组立即给予同体积生理盐水。观察各组大鼠惊厥潜伏期和惊厥持续时间;末次惊厥24 h后检测血清白细胞介素-1,6,8(IL-1,IL-6,IL-8),肿瘤坏死因子-α(TNF-α),干扰素-α(IFN-α)水平及脑组织匀浆中环磷酸腺苷(cAMP),前列腺素E2(PGE2)水平。结果:龙胆碱高、低剂量组大鼠惊厥潜伏期明显长于模型组(P<0.05);惊厥持续时间明显短于模型组(P<0.01)。(P<0.05);龙胆碱高、低剂量组血清IL-1,IL-6,IL-8,TNF-α,脑组织PGE2水平明显低于模型组(P<0.05)且高剂量组低于低剂量组(P<0.05)。结论:龙胆碱具有解热抗惊厥作用,其作用机制与体内细胞因子改变进而影响下丘脑PGE2水平相关。
Objective: To investigate the anticonvulsant mechanism of gentianin in rats with recurrent febrile seizures. Methods: Sixty Sprague-Dawley rats were randomly divided into healthy control group, model group, gentian high and low dose groups, 15 rats in each group. Except for the healthy control group, the other rats were made according to the literature method to make the rat model of febrile seizures. Rats were induced seizures every other day, a total of 10 induced, 20 d. Gentian high and low dose groups were given gentian, saline immediately after each convulsion 200,50 mg.kg-1, ip, model group and healthy control group immediately given the same volume of saline. The latency of seizures and the duration of seizures were observed in each group. Serum levels of IL-1, IL-6, IL-8, TNF- α, IFN-α and cAMP and prostaglandin E2 (PGE2) levels in brain homogenate were measured. Results: Seizure latency of gentian high and low dose groups was significantly longer than that of model group (P <0.05). Duration of seizure was significantly shorter than that of model group (P <0.01). (P <0.05). The serum levels of IL-1, IL-6, IL-8, TNF-α and PGE2 in the gentian and low dose groups were significantly lower than those in the model group (P <0.05) In low dose group (P <0.05). Conclusion: Chlordiazepoxide has antipyretic and anticonvulsant effects, and its mechanism of action is related to the change of cytokines in vivo and the PGE2 level in the hypothalamus.