过量补充蛋氨酸会加剧大鼠腹主动脉瘤的发展。

Excessive Methionine Supplementation Exacerbates the Development of Abdominal Aortic Aneurysm in Rats.

作者信息

Fan Yichuan, Li Nan, Liu Chengwei, Dong Haipeng, Hu Xinhua

机构信息

Department of Vascular and Thyroid Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.

Division of Vascular Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, China.

出版信息

J Vasc Res. 2019;56(5):230-240. doi: 10.1159/000501313. Epub 2019 Jul 15.

Abstract

OBJECTIVE

The relationship between methionine (Met) and abdominal aortic aneurysm (AAA) has been previously demonstrated, but the mechanisms controlling this association remain unclear. This study investigated the potential contribution of hypermethioninemia (HMet) to the development of AAA.

METHODS

A model of AAA was induced by intraluminal porcine pancreatic elastase (PPE) infusion in 60 male Sprague-Dawley rats divided into 4 groups (n = 15 per group). Met was supplied by intragastric administration (1 g/kg body weight/day) from 1 week before surgery until 4 weeks after surgery. The aortic diameter was measured by ultrasound. Aortas were collected 4 weeks after surgery and subjected to biochemical analysis, histological assays, and transmission electron microscopy.

RESULTS

After 5 weeks of Met supplementation, HMet increased the dilation ratio of the HMet + PPE group, and hyperhomocysteinemia was also induced in HMet and HMet + PPE rats. Increased matrix metalloproteinase-2 (MMP-2), osteopontin, and interleukin-6 expression was detected in HMet + PPE rats. Furthermore, increased autophagy was detected in the HMet + PPE group.

CONCLUSION

This study demonstrates that HMet may exacerbate the formation of AAA due to the increased dilation ratio partially via enhancing MMP-2 and inflammatory responses.

摘要

目的

蛋氨酸(Met)与腹主动脉瘤(AAA)之间的关系此前已有报道,但控制这种关联的机制仍不清楚。本研究调查了高蛋氨酸血症(HMet)对AAA发生发展的潜在影响。

方法

将60只雄性Sprague-Dawley大鼠分为4组(每组n = 15),通过腔内注射猪胰弹性蛋白酶(PPE)诱导建立AAA模型。从手术前1周开始至手术后4周,通过胃内给药(1 g/kg体重/天)提供Met。用超声测量主动脉直径。术后4周收集主动脉,进行生化分析、组织学检测和透射电子显微镜检查。

结果

补充Met 5周后,HMet增加了HMet + PPE组的扩张率,HMet组和HMet + PPE组大鼠也出现了高同型半胱氨酸血症。在HMet + PPE组大鼠中检测到基质金属蛋白酶-2(MMP-2)、骨桥蛋白和白细胞介素-6表达增加。此外,在HMet + PPE组中检测到自噬增加。

结论

本研究表明,HMet可能部分通过增强MMP-2和炎症反应导致扩张率增加,从而加剧AAA的形成。

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