[血栓形成相关基因缺陷的协同效应]

[Synergistic effect of deficiency in thrombosis-related genes].

作者信息

Shen Yue-chun, Luo Bi-hui, Ou Bi-ru, Chen Ai-lan, Wang Xiao-ming, Li Jun

机构信息

Department of Cardiology, First Affiliated Hospital, Guangzhou Medical College, Guangzhou, Guangdong, 510120 PR China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010 Jun;27(3):246-9. doi: 10.3760/cma.j.issn.1003-9406.2010.0.002.

DOI:10.3760/cma.j.issn.1003-9406.2010.0.002

PMID:20533258

Abstract

OBJECTIVE

To investigate the interaction of deficiency in thrombosis-related gene in a mouse model.

METHODS

To generate mice carrying mutations in alpha-galactosidase A (Gla) and factor V Leiden (Fvl) and analyze the phenotypes, namely, tissue fibrin deposition and thrombus formation in organs.

RESULTS

Fibrin deposition in organs of mice carrying both mutations in Gla and Fvl was significantly increased compared with that in mice with single mutaton: [Gla(-/0) Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(-/0)Fv(+/+)]=(0.28+/-0.03)% vs.(0.07+/-0.007)%, P<0.01; [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(+/0)Fv(Q/Q)+Gla(+/+)Fv(Q/Q)]=(0.28+/-0.03)% vs.(0.11+/-0.02)%, P< 0.01. Meanwhile, the number of thrombi on organ sections of mice carrying both mutations in Gla and Fvl was significantly increased compared with the single mutation carrier: [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(-/0)Fv(+/+)]=1.9+/-0.7 vs. 0.0+/-0.0, P<0.05; [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs. [Gla(+/0)Fv(Q/Q)+Gla(+/+)Fv(Q/Q)]=1.9+/-0.7 vs. 0.3+/-0.1, P<0.05.

CONCLUSION

These observations demonstrated that there was synergistic effect in Gla and Fvl deficiency in mice. It suggested that there could be a combination of GLA deficiency and FVL or other thrombosis-related gene defect in patients with genetic severe early-onset thrombosis.

摘要

目的

在小鼠模型中研究血栓形成相关基因缺陷的相互作用。

方法

培育携带α-半乳糖苷酶A（Gla）和凝血因子V莱顿（Fvl）突变的小鼠，并分析其表型，即器官中的组织纤维蛋白沉积和血栓形成情况。

结果

与单一突变小鼠相比，同时携带Gla和Fvl两种突变的小鼠器官中的纤维蛋白沉积显著增加：[Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] 与 [Gla(-/0)Fv(+/+)] 相比 = (0.28±0.03)% 与 (0.07±0.007)%，P<0.01；[Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] 与 [Gla(+/0)Fv(Q/Q)+Gla(+/+)Fv(Q/Q)] 相比 = (0.28±0.03)% 与 (0.11±0.02)%，P<0.01。同时，与单一突变携带者相比，同时携带Gla和Fvl两种突变的小鼠器官切片上的血栓数量显著增加：[Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] 与 [Gla(-/0)Fv(+/+)] 相比 = 1.9±0.7 与 0.0±0.0，P<0.05；[Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] 与 [Gla(+/0)Fv(Q/Q)+Gla(+/+)Fv(Q/Q)] 相比 = 1.9±0.7 与 0.3±0.1，P<0.05。