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柚苷对大鼠创伤性脑损伤的预防治疗价值及其机制研究

Naringin Benefits the Recovery of Rats with Traumatic Brain Injury Through Attenuating Oxidative Stress and Inflammation

【作者】 崔群建

【导师】 赵洪洋;

【作者基本信息】 华中科技大学 , 外科学, 2010, 博士

【摘要】 目的拟通过动物实验研究柚苷对脑外伤的预防治疗价值及其可能机制。方法大鼠随机平均分为4组。A组(对照组),除不进行打击外,其余操作同模型组;B组(模型组),自由落体打击法制作脑外伤大鼠模型。C组(柚苷术后干预组),造模后给予柚苷(50mg/kg)治疗7d;D组(柚苷预防治疗组),提前7d给予大鼠柚苷,在造模后继续给药7d。术后通过尼氏染色观察坏死灶体积,干湿重法测定脑损伤皮层含水量,并对大鼠进行行为学评分;生物化学法测定脑皮层和血清中SOD和MDA的含量;免疫荧光观察损伤皮层il-1β和iNOS的表达,western blot观察损伤皮层il-1β的含量,生物化学法检测损伤皮层iNOS的活性和NO的含量。结果与A组相比,B组在成模后损伤皮层含水量增高(损伤1d),坏死灶出现,与损伤正相关的神经功能评分较高。与B组相比,柚苷干预明显降低了脑组织含水量,坏死灶体积,降低了神经功能评分。与C组相比,D组作用更为明显,降低组织含水量的作用出现早,梗死体积更小,神经功能评分低;与A组相比,B组大鼠损伤脑组织和血液中出现显著的MDA含量增高,SOD活性降低;损伤脑皮层的iL-1β表达显著升高,iNOS活性增强,NO含量增加。与B组相比,柚苷干预缓解了上述改变。与C组相比,D组的作用更为明显。以上各组有显著性差异(P<0.01)。结论脑外伤后大鼠出现氧化应激平衡失调和炎症的加剧,可能与脑外伤后的继发性损伤有关。柚苷干预有利于减轻大鼠脑外伤后的神经病理损害,促进功能恢复。柚苷的保护作用可能与缓解脑外伤后的氧化应激和炎症有关。与单纯术后干预相比,复合预防性给药更有利于柚苷保护作用的发挥。

【Abstract】 Objective:To study the role of naringin in treating rats with traumatic brain injury (TBI) and its possible mechanism.Methods:Rats were randomly separated into four groups. Rats in group A were sham-operated; in group B received TBI operation; in group C were treated with naringin for 7 days after TBI; while naringin were given continually for 7 days either pro-or post-TBI. The TBI was induced by weight drop technique and naringin was given orally 50mg/kg per day. Volume of damaged cortex, tissue water content, neurological score, SOD and MDA in serum and damaged brain cortex, il-1βand iNOS expression in cortex, as well as NO, were detected with respective methods.Results:Comparing with group A, rats in group B showed significant brain edema, bigger volume of damaged brain cortex, and obviously sensor motor dysfunction. However, the brain edema and damage volume were reduced and behaviors was improved in rats of group C and D, comparing with rats in group B. Measurement of SOD and MDA showed that naringin elevated the activity of SOD, and reduced MDA content both in injured brain cortex and serum. And, the expression of il-1βand iNOS, as well as NO were reduced by naringin, since the obvious elevation of them appeared after TBI. Meanwhile, all those changes were more significant in group D than in group C.Conclusion:Oxidative damage and inflammation were enhanced after TBI, which seems to be important factors for secondary brain damage. Naringin treatment can attenuate the neuropathological damages and improve the functional recovery of rats after TBI, partly through weakening oxidative damage and inflammation. Comparing with treatment post-TBI, naringin also given as prophylactic treatment shows better effect on protecting brain.

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