高脂肪饮食加剧小鼠脑卒中模型中的脑梗死、出血性转化和神经炎症。

High-Fat Diet Aggravates Cerebral Infarct, Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model.

机构信息

Diabète Athérothrombose Thérapies Réunion Océan Indien, INSERM, UMR 1188, Université de La Réunion, 2 rue Maxime Rivière, 97400 Sainte-Clotilde, La Réunion, France.

CHU de la Réunion, Service de Neuroréanimation, 97410 Saint-Pierre de la Réunion, La Réunion, France.

出版信息

Int J Mol Sci. 2021 Apr 27;22(9):4571. doi: 10.3390/ijms22094571.

BACKGROUND

Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet.

METHODS

Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated.

RESULTS

HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30-46.7%) vs. 28.45 (IQR 21-30%); = 0.016) and HT (HFD: 2 (IQR 1-5) vs. ND: 0 (IQR 0-1); = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group.

CONCLUSION

Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.

背景

2 型糖尿病（T2D）患者发生中风的后果比非糖尿病患者更差。我们旨在建立一种新的、可重现的高脂肪饮食诱导的糖耐量受损情况下的中风小鼠模型。

方法

成年 C57BL6 小鼠用正常饮食（ND）或高脂肪饮食（HFD）喂养 2 个月。我们采用大脑中动脉闭塞（MCAO）模型，缺血 90 分钟。口服葡萄糖耐量试验（OGTT）和胰岛素耐量试验（ITT）用于评估糖尿病前期状态。评估脑梗死体积、出血转化（HT）以及全身和脑炎症标志物。

结果

HFD 喂养后，小鼠体重和 OGTT 后血糖升高。与 ND 组相比，HFD 组的脑梗死体积显著增加（38.7（IQR 30-46.7%）vs. 28.45（IQR 21-30%）；=0.016）和 HT 发生率更高（HFD：2（IQR 1-5）vs. ND：0（IQR 0-1）；=0.012），并且梗死半球中 IL-6 和 MCP-1 水平更高。