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主动脉夹层动脉瘤中白细胞介素-1β的局部上调:与基质金属蛋白酶-2、9表达及生物力学降低的相关性

Local upregulation of interleukin-1 beta in aortic dissecting aneurysm: correlation with matrix metalloproteinase-2, 9 expression and biomechanical decrease.

作者信息

Jiang Yun-Fei, Guo Ling-Ling, Zhang Li-Wei, Chu Yong-Xin, Zhu Guang-Lang, Lu Ye, Zhang Lei, Lu Qing-Sheng, Jing Zai-Ping

机构信息

Department of Vascular Surgery, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.

Department of Biological Therapies for Cancer, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

出版信息

Interact Cardiovasc Thorac Surg. 2019 Mar 1;28(3):344-352. doi: 10.1093/icvts/ivy256.

Abstract

OBJECTIVES

Our goal was to examine whether interleukin-1 beta (IL-1β) originates locally and its possible relationship with matrix metalloproteinases (MMPs), apoptosis, elastin fibres and biomechanics in aortic dissecting aneurysms (DAs).

METHODS

Aortic DAs were induced in 24 rats with β-aminopropionitrile (BAPN); another 12 rats without BAPN were designated as controls. Then IL-1β levels were measured both in the circulation and in local aortic specimens. The expression of MMP-2 and MMP-9 and Victoria blue and TUNEL staining were also detected. Biomechanical parameters such as the elasticity modulus were used to detect the biomechanical changes in the aortic wall. The correlation of IL-1β, MMP-2, MMP-9, apoptosis and biomechanical properties was analysed.

RESULTS

Seventeen rats (17/24, 71%) in the BAPN-treated group died of DA rupture. IL-1β levels were dramatically increased in the DA specimens but not in the circulation. Victoria blue staining confirmed the formation of the DA and the reduction of elastin content after induction by BAPN. The extent of apoptosis in the aortic media was dramatically higher in rats with BAPN-induced DA than that in the control group and that in rats treated with BAPN but without DA. MMP-2 and MMP-9 levels were significantly increased in BAPN-treated rats compared to the controls, but no statistical significance was found between rats with and without DA. There were significant differences in biomechanical parameters, such as the elasticity modulus. Among the 3 groups, IL-1β was positively correlated with MMP-2 and MMP-9 levels and with the elasticity modulus but not with apoptosis.

CONCLUSIONS

Local IL-1β might participate in the formation of aortic DA through the upregulation of MMP-2 and MMP-9 and the breakage of elastin fibres, which finally weakens the biomechanical properties of the aortic wall.

摘要

目的

我们的目标是研究白细胞介素-1β(IL-1β)是否在局部产生,以及它与主动脉夹层动脉瘤(DA)中基质金属蛋白酶(MMPs)、细胞凋亡、弹性纤维和生物力学之间的可能关系。

方法

用β-氨基丙腈(BAPN)诱导24只大鼠形成主动脉DA;另外12只未用BAPN的大鼠作为对照。然后检测循环系统和局部主动脉标本中的IL-1β水平。还检测了MMP-2和MMP-9的表达以及维多利亚蓝和TUNEL染色。使用弹性模量等生物力学参数来检测主动脉壁的生物力学变化。分析了IL-1β、MMP-2、MMP-9、细胞凋亡和生物力学特性之间的相关性。

结果

BAPN治疗组中有17只大鼠(17/24,71%)死于DA破裂。DA标本中的IL-1β水平显著升高,但循环系统中未升高。维多利亚蓝染色证实了DA的形成以及BAPN诱导后弹性蛋白含量的减少。BAPN诱导DA的大鼠主动脉中膜的细胞凋亡程度明显高于对照组以及用BAPN治疗但未发生DA的大鼠。与对照组相比,BAPN治疗的大鼠中MMP-2和MMP-9水平显著升高,但有DA和无DA的大鼠之间未发现统计学差异。生物力学参数如弹性模量存在显著差异。在3组中,IL-

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