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阿托伐他汀对大鼠创伤性脑损伤后的疗效

Atorvastatin efficiency after traumatic brain injury in rats.

作者信息

Turkoglu Omer Faruk, Eroglu Hakan, Okutan Ozerk, Gurcan Oktay, Bodur Ebru, Sargon Mustafa F, Oner Levent, Beskonakl i Etem

机构信息

Department of Neurological Surgery, Ankara Ataturk Research and Education Hospital, Bilkent, 06800 Ankara, Turkey.

出版信息

Surg Neurol. 2009 Aug;72(2):146-52; discussion 152. doi: 10.1016/j.surneu.2008.07.004. Epub 2008 Sep 11.

Abstract

BACKGROUND

The neuroprotective effects of statins possibly depend on their pleiotropic effect such as antioxidative and anti-inflammatory properties. In this study, we have evaluated the efficiency of atorvastatin on brain edema, lipid peroxidation, and ultrastructural changes in TBI animal model.

METHODS

Modified Feeney method has been used for the trauma model in rats. Only craniectomy for group A and trauma after craniectomy for group B was the procedure for animals. For the trauma, rods weighing 24 g were dropped on a foot plate just over the dura. Atorvastatin (1 mg/kg, IP) was administered to the animals in group C after craniectomy and trauma; but on the other hand, animals in group D received only 0.5 mL PEG as the vehicle. Brains were harvested 24 hours after the trauma for the assays of wet-dry weight, lipid peroxidation level, and ultrastructural investigations. Lipid peroxidation levels, TEM, and UNGS were the investigated parameters. The statistical comparisons between the groups were investigated by 1-way ANOVA and post hoc analysis by Duncan and Dunnett T3 test within the groups at the significance level P = .05.

RESULTS

Trauma increased water contents of the brain tissues and lipid peroxidation levels in groups B and D. When compared with the results of group B (brain edema, 84.694% +/- 1.510%; lipid peroxidation, 74.932 +/- 2.491 nmol/g tissue), atorvastatin (1 mg/kg) significantly decreased brain edema (77.362% +/- 1.448%), lipid peroxidation level (58.335 +/- 3.980 nmol/g tissue), and UNGS scores in group C (P < 0.05).

CONCLUSION

In this descriptive study, the remarkable improvements of atorvastatin on brain edema, lipid peroxidation, and ultrastructural investigations encouraged us for a further dose optimization study.

摘要

背景

他汀类药物的神经保护作用可能取决于其多效性,如抗氧化和抗炎特性。在本研究中,我们评估了阿托伐他汀对创伤性脑损伤(TBI)动物模型脑水肿、脂质过氧化和超微结构变化的疗效。

方法

采用改良的Feeney法建立大鼠创伤模型。A组动物仅行颅骨切除术,B组动物在颅骨切除术后进行创伤。创伤时,将重24 g的铁棒落在硬脑膜上方的脚板上。C组动物在颅骨切除和创伤后给予阿托伐他汀(1 mg/kg,腹腔注射);而D组动物仅接受0.5 mL聚乙二醇作为赋形剂。创伤后24小时采集脑组织进行干湿重测定、脂质过氧化水平检测和超微结构研究。检测参数包括脂质过氧化水平、透射电子显微镜(TEM)和未加权神经功能缺损评分(UNGS)。组间统计比较采用单因素方差分析,并在显著性水平P = 0.05时,通过Duncan和Dunnett T3检验进行组内事后分析。

结果

创伤增加了B组和D组脑组织的含水量和脂质过氧化水平。与B组结果(脑水肿,84.694% +/- 1.510%;脂质过氧化,74.932 +/- 2.491 nmol/g组织)相比,阿托伐他汀(1 mg/kg)显著降低了C组的脑水肿(77.362% +/- 1.448%)、脂质过氧化水平(58.335 +/- 3.980 nmol/g组织)和UNGS评分(P < 0.05)。

结论

在本描述性研究中,阿托伐他汀在脑水肿、脂质过氧化和超微结构研究方面的显著改善促使我们进行进一步的剂量优化研究。

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