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他汀类药物预处理可保护糖尿病小鼠的大脑免受局灶性脑缺血的影响。

Statin pre-treatment protects brain against focal cerebral ischemia in diabetic mice.

作者信息

Cakmak Atil, Yemişçi Müge, Köksoy Cüneyt, Yazgan Uğur, Dinçer Deniz, Dalkara Turgay

机构信息

Department of General Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey.

出版信息

J Surg Res. 2007 Apr;138(2):254-8. doi: 10.1016/j.jss.2006.06.012. Epub 2007 Feb 2.

Abstract

BACKGROUND

Cerebrovascular diseases and other vascular complications are common and cause considerable mortality and morbidity in diabetes mellitus. Recent studies suggest that statins reduce the incidence of stroke in diabetic as well as non-diabetic patients. The outcome of stroke is shown to be worse in diabetics. However, the effect of statins on the outcome of stroke occurring in diabetics is not clear. The purpose of this study was to investigate the effect of pre-treatment with statins on focal cerebral ischemia in diabetic mice.

MATERIALS AND METHODS

Swiss albino mice were randomized into two groups. Diabetes was induced in the first group by intravenous streptozotosin injection. The second group served as non-diabetic. After 4 weeks, half of the mice in diabetic and non-diabetic groups were randomized to receive intraperitoneal simvastatin 1 mg/kg/day or saline treatment for 14 days. Subsequently, mice were subjected to 90 min of proximal middle cerebral artery occlusion and 24 h of reperfusion. Sham-operation was also performed for each group. After 24 h of reperfusion, neurological deficits were scored and the infarct volume was measured on Nissl stained brain sections.

RESULTS

Infarct volume (median, interquartile range) was significantly increased in the diabetic group (60.7 mm(3)) compared to non-diabetic group (53.4 mm(3)). Statin pre-treatment significantly reduced the infarct volume (to 40.4; 33.5 mm(3), respectively) and neurological disability scores both in diabetic and non-diabetic groups.

CONCLUSIONS

These data suggest that diabetes aggravates the ischemic damage after focal cerebral ischemia and statin pre-treatment protects the brain in diabetic as well as healthy animals. Statin treatment may favorably affect stroke outcome in diabetic patients in addition to decreasing stroke incidence.

摘要

背景

脑血管疾病和其他血管并发症在糖尿病患者中很常见,会导致相当高的死亡率和发病率。最近的研究表明,他汀类药物可降低糖尿病患者和非糖尿病患者中风的发生率。糖尿病患者中风的预后更差。然而,他汀类药物对糖尿病患者中风预后的影响尚不清楚。本研究的目的是探讨他汀类药物预处理对糖尿病小鼠局灶性脑缺血的影响。

材料与方法

将瑞士白化小鼠随机分为两组。第一组通过静脉注射链脲佐菌素诱导糖尿病。第二组作为非糖尿病组。4周后,将糖尿病组和非糖尿病组中的一半小鼠随机分为接受腹腔注射辛伐他汀1mg/kg/天或生理盐水治疗14天。随后,对小鼠进行90分钟的大脑中动脉近端闭塞和24小时的再灌注。每组也进行假手术。再灌注24小时后,对神经功能缺损进行评分,并在尼氏染色的脑切片上测量梗死体积。

结果

与非糖尿病组(53.4mm³)相比,糖尿病组的梗死体积(中位数,四分位间距)显著增加(60.7mm³)。他汀类药物预处理显著降低了糖尿病组和非糖尿病组的梗死体积(分别降至40.4;33.5mm³)和神经功能障碍评分。

结论

这些数据表明,糖尿病会加重局灶性脑缺血后的缺血性损伤,他汀类药物预处理对糖尿病动物和健康动物的大脑均有保护作用。除了降低中风发生率外,他汀类药物治疗可能对糖尿病患者的中风预后产生有利影响。

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