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β-细辛脑对阿尔茨海默病大鼠脑血管的保护作用:行为学、脑血流、生化及基因研究。

Cerebrovascular protection of β-asarone in Alzheimer's disease rats: a behavioral, cerebral blood flow, biochemical and genic study.

机构信息

The First People's Hospital of Taizhou city, Taizhou, Zhejiang, China.

出版信息

J Ethnopharmacol. 2012 Nov 21;144(2):305-12. doi: 10.1016/j.jep.2012.09.013. Epub 2012 Sep 15.

Abstract

AIM OF THE STUDY

Recent studies have suggested that β-asarone have neuroprotective and cardiovascular protective effects in animal model. However, the influence of β-asarone on cerebrovascular system has not been explored so far. Therefore, present study was designed to determine whether repeated exposures to β-asarone resulted in positive effects on cerebrovascular function in AD rats.

MATERIALS AND METHODS

Alzheimer's disease induced rats was established by injecting both D-galactose (D-gal) and aluminum chloride (AlCl(3)) into abdominal cavity for 42 days. After injection of AlCl(3) and D-gal or saline for 28 days, the rats were treated with volume-matched vehicle or β-asarone (25mg/kg, 50mg/kg or 100mg/kg, i.h.) or Nimodipine (40mg/kg, i.g) once daily for consecutive 14 days, respectively. Behavioral responses of animals were assessed in a Morris water maze. CBF was measured by laser Doppler flowmetry. At the end of this period all rats were sacrificed, lactic acid, pyruvic acid content, Na+K+ATPase activity were determined in brain tissue homogenate to estimate the brain biochemical changes and mRNA expression of ET-1, eNOS and APP was measured with real-time RT-PCR method.

RESULTS

The spatial navigation task latencies, the times through platform zone and the time for the first through platform zone in the target quadrant in probe task, rCBF of right parietal lobe, the contents of lactic acid, pyruvic acid, and the activity of Na-K-ATP of cortex, and ET-1 and eNOS mRNA expression in hippocampus of AG rats were different from those of BG, P<0.05; The level of APP mRNA expression in model control group rats was higher than that in BG, though there was not a statistically significant difference, P>0.05; Compared with AG, HG rats spatial navigation task latencies were shorter, in probe task the times through platform zone in the target quadrant were bigger, rCBF and blood cell concentration of right parietal lobe were higher, the contents of pyruvic acid was lower, the activity of Na-K-ATP was higher, and ET-1 mRNA expression in hippocampus was lower, P<0.05; The level of eNOS and APP mRNA expression in HG rats was lower than that in AG, though there was not a statistically significant difference, P>0.05;

CONCLUSION

The present results suggested that β-asarone may be useful in memory impairment due to its cerebrovascular protection in AD rats and may develop as a therapeutic drug for treatment of AD patients.

摘要

目的

最近的研究表明,β-细辛脑在动物模型中具有神经保护和心血管保护作用。然而,β-细辛脑对脑血管系统的影响尚未得到探索。因此,本研究旨在确定重复暴露于β-细辛脑是否会对 AD 大鼠的脑血管功能产生积极影响。

材料和方法

通过向腹腔内注射半乳糖(D-gal)和氯化铝(AlCl(3))42 天,建立阿尔茨海默病诱导大鼠模型。在注射 AlCl(3)和 D-gal 或生理盐水 28 天后,将大鼠分别用体积匹配的载体或β-细辛脑(25mg/kg、50mg/kg 或 100mg/kg,i.h.)或尼莫地平(40mg/kg,i.g.)处理,连续 14 天。通过 Morris 水迷宫评估动物的行为反应。通过激光多普勒血流仪测量 CBF。在这段时间结束时,所有大鼠均被处死,测量脑组织匀浆中的乳酸、丙酮酸含量、Na+K+ATP 酶活性,以评估脑生化变化,并采用实时 RT-PCR 法测量 ET-1、eNOS 和 APP 的 mRNA 表达。

结果

AG 大鼠的空间导航任务潜伏期、目标象限平台区通过次数和首次通过平台区时间、右顶叶 rCBF、皮质乳酸、丙酮酸含量和 Na-K-ATP 活性以及海马 ET-1 和 eNOS mRNA 表达与 BG 大鼠不同,P<0.05;模型对照组大鼠 APP mRNA 表达水平高于 BG 组,但无统计学差异,P>0.05;与 AG 相比,HG 大鼠的空间导航任务潜伏期较短,在目标象限的平台区通过次数较多,右顶叶 rCBF 和血细胞浓度较高,丙酮酸含量较低,Na-K-ATP 活性较高,海马 ET-1 mRNA 表达较低,P<0.05;HG 大鼠的 eNOS 和 APP mRNA 表达水平低于 AG 大鼠,虽无统计学差异,P>0.05。

结论

本研究结果表明,β-细辛脑可能通过对 AD 大鼠的脑血管保护作用,对记忆障碍具有治疗作用,可能成为治疗 AD 患者的治疗药物。

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