[辛伐他汀对动脉粥样硬化大鼠高迁移率族蛋白B1表达的影响]

[The effect of simvastatin on the expression of high mobility group box-1 protein in atherosclerotic rats].

作者信息

Yin Ya-xin, Yao Yong-ming, Liu Run-mei, Zhai Hong-xia, Li Liang, Zhang Jin-jin, Chen Hai-wei, Wang Lei, Li Na, Xia Yun-feng

机构信息

First Affiliated Hospital of General Hospital of PLA, Beijing 100048, China.

出版信息

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2010 May;22(5):306-8.

PMID:20519084

Abstract

OBJECTIVE

To observe the effect of simvastatin on the expression of high mobility group box-1 protein (HMGB1) and morphology of atherosclerotic plaques in atherosclerotic rats, to ascertain whether HMGB1 plays a role in the preventive mechanism of simvastatin from atherosclerosis (AS).

METHODS

Sixty Wistar rats were divided randomly into three groups: control group, model group and simvastatin treatment group. Gastric gavage of vitamin D3 with high fat food was used to reproduce atherosclerotic rat model. The rats in the treatment group were treated with simvastatin of 2.5 mg x kg(-1) x d(-1) (gastric perfusion) 8 weeks after fat diet. The expression of the histopathology and protein of HMGB1 in atherosclerotic plaques of the aorta was observed by immunohistochemistry at 10 weeks and 12 weeks. The gene expression of HMGB1 at atherosclerotic plaques of aorta was observed with real time-polymerase chain reaction (RT-PCR). The morphology of the atherosclerotic plaques was observed.

RESULTS

The expression of HMGB1 increased significantly in atherosclerotic plaques in model group, and simvastatin could evidently inhibit the expression of HMGB1, and it was more obvious in 12-week group. Compared with control group, the HMGB1 mRNA expression was upregulated in all atherosclerotic model groups (10 weeks: 19.695+/- 1.418 vs. 2.981+/-0.753, 12 weeks: 20.542+/-1.132 vs. 3.219+/-0.332, both P<0.01). In the simvastatin treatment group, the gene expression of HMGB1 was lower than the age-match model group at 10 weeks (15.798+/-0.891) and 12 weeks (12.641+/-0.734), and in the 12-week treatment group it was lower than that in the 10-week treatment group (P<0.05 or P<0.01). In the model group, the ring-shape calcified atherosclerotic plaques were extensively found in the wall of the aorta. Simvastatin could obviously inhibit the formation of the atherosclerotic plaques, and the effect was more obvious in the 12-week treatment group than that of the 10-week treatment group.

CONCLUSION

Simvastatin can alleviate the formation of the atherosclerotic plaques in the atherosclerotic rats, decrease the protein and mRNA expression of HMGB1. The results suggest that the vessels are protected from forming AS through alleviating inflammatory reaction.

摘要

目的

观察辛伐他汀对动脉粥样硬化大鼠高迁移率族蛋白B1（HMGB1）表达及动脉粥样硬化斑块形态的影响，以明确HMGB1在辛伐他汀预防动脉粥样硬化（AS）机制中是否发挥作用。

方法

将60只Wistar大鼠随机分为三组：对照组、模型组和辛伐他汀治疗组。采用高脂饲料灌胃维生素D3的方法建立动脉粥样硬化大鼠模型。造模8周后，治疗组大鼠给予辛伐他汀2.5mg·kg⁻¹·d⁻¹（灌胃）。在第10周和第12周时，通过免疫组化观察主动脉粥样硬化斑块中HMGB1的组织病理学及蛋白表达。采用实时聚合酶链反应（RT-PCR）观察主动脉粥样硬化斑块中HMGB1的基因表达。观察动脉粥样硬化斑块的形态。

结果

模型组动脉粥样硬化斑块中HMGB1表达显著增加，辛伐他汀可明显抑制HMGB1表达，在12周组更为明显。与对照组相比，各动脉粥样硬化模型组HMGB1 mRNA表达均上调（10周：19.695±1.418 vs. 2.981±0.753，12周：20.542±1.132 vs. 3.219±0.332，均P<0.01）。在辛伐他汀治疗组，10周（15.798±0.891）和12周（12.641±0.734）时HMGB1基因表达低于同年龄模型组，且12周治疗组低于10周治疗组（P<0.05或P<0.01）。模型组主动脉壁广泛发现环形钙化动脉粥样硬化斑块。辛伐他汀可明显抑制动脉粥样硬化斑块形成，12周治疗组效果比10周治疗组更明显。