中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2010年
3期
246-249
,共4页
沈粤春%罗碧辉%区碧如%陈爱兰%王晓明%李君
瀋粵春%囉碧輝%區碧如%陳愛蘭%王曉明%李君
침월춘%라벽휘%구벽여%진애란%왕효명%리군
α-半乳糖苷酶A%凝血因子V%点突变%纤维蛋白%血栓
α-半乳糖苷酶A%凝血因子V%點突變%纖維蛋白%血栓
α-반유당감매A%응혈인자V%점돌변%섬유단백%혈전
α-galactosidase A%factor V Leiden%mutation%fibrin%thrombosis
目的 探讨血栓相关基因缺陷之间在体内的相互作用.方法 由α-半乳糖苷酶A(α-galactosidase A,Gla)缺乏和凝血因子V Leiden(factor V I.eiden,Fvl)基因突变小鼠建立二者复合基因突变小鼠,通过器官组织学分析,评价致病基因表现型-纤维蛋白沉积和血栓形成情况.结果 Gla缺乏与Fvl复合基因突变小鼠的器官纤维蛋白沉积较二者之一单独突变明显增加.复合突变比Gla缺乏=Gla/0FvQ/Q和Gla/FvQ/Q 比Gla-/0 Fv+/+=(0.28±0.03)%vs.(0.07±0.007)%,P<0.01;复合突变比Fvl 突变=Gla/0FvQ/Q和Gla-/- FvQ/Q 比Gla+/0 FvQ/Q和Gla+/+ FvQ/Q=(0.28±0.03)%vs.(0.11±0.02)%,P<0.01.同时,Gla缺乏与Fvl复合基因突变小鼠的器官断面血栓形成数日也分别较二者之一明显增加.复合突变比Gla缺乏=1.9±0.7 vs.0.0±0.0,P<0.05;复合突变比Fvl突变=1.9±0.7 vs.0.3±0.1,P<0.05.结论 Gla缺乏与Fvl突变在小鼠体内相互加重血栓前状态和血栓形成,临床上GLA缺乏、FVL突变或其它血栓相关基因缺陷患者出现早发和严重的血栓疾病可能合并其它遗传性血栓相关的基因缺陷.
目的 探討血栓相關基因缺陷之間在體內的相互作用.方法 由α-半乳糖苷酶A(α-galactosidase A,Gla)缺乏和凝血因子V Leiden(factor V I.eiden,Fvl)基因突變小鼠建立二者複閤基因突變小鼠,通過器官組織學分析,評價緻病基因錶現型-纖維蛋白沉積和血栓形成情況.結果 Gla缺乏與Fvl複閤基因突變小鼠的器官纖維蛋白沉積較二者之一單獨突變明顯增加.複閤突變比Gla缺乏=Gla/0FvQ/Q和Gla/FvQ/Q 比Gla-/0 Fv+/+=(0.28±0.03)%vs.(0.07±0.007)%,P<0.01;複閤突變比Fvl 突變=Gla/0FvQ/Q和Gla-/- FvQ/Q 比Gla+/0 FvQ/Q和Gla+/+ FvQ/Q=(0.28±0.03)%vs.(0.11±0.02)%,P<0.01.同時,Gla缺乏與Fvl複閤基因突變小鼠的器官斷麵血栓形成數日也分彆較二者之一明顯增加.複閤突變比Gla缺乏=1.9±0.7 vs.0.0±0.0,P<0.05;複閤突變比Fvl突變=1.9±0.7 vs.0.3±0.1,P<0.05.結論 Gla缺乏與Fvl突變在小鼠體內相互加重血栓前狀態和血栓形成,臨床上GLA缺乏、FVL突變或其它血栓相關基因缺陷患者齣現早髮和嚴重的血栓疾病可能閤併其它遺傳性血栓相關的基因缺陷.
목적 탐토혈전상관기인결함지간재체내적상호작용.방법 유α-반유당감매A(α-galactosidase A,Gla)결핍화응혈인자V Leiden(factor V I.eiden,Fvl)기인돌변소서건립이자복합기인돌변소서,통과기관조직학분석,평개치병기인표현형-섬유단백침적화혈전형성정황.결과 Gla결핍여Fvl복합기인돌변소서적기관섬유단백침적교이자지일단독돌변명현증가.복합돌변비Gla결핍=Gla/0FvQ/Q화Gla/FvQ/Q 비Gla-/0 Fv+/+=(0.28±0.03)%vs.(0.07±0.007)%,P<0.01;복합돌변비Fvl 돌변=Gla/0FvQ/Q화Gla-/- FvQ/Q 비Gla+/0 FvQ/Q화Gla+/+ FvQ/Q=(0.28±0.03)%vs.(0.11±0.02)%,P<0.01.동시,Gla결핍여Fvl복합기인돌변소서적기관단면혈전형성수일야분별교이자지일명현증가.복합돌변비Gla결핍=1.9±0.7 vs.0.0±0.0,P<0.05;복합돌변비Fvl돌변=1.9±0.7 vs.0.3±0.1,P<0.05.결론 Gla결핍여Fvl돌변재소서체내상호가중혈전전상태화혈전형성,림상상GLA결핍、FVL돌변혹기타혈전상관기인결함환자출현조발화엄중적혈전질병가능합병기타유전성혈전상관적기인결함.
Objective To investigate the interaction of deficiency in thrombosis-related gene in a mouse model. Methods To generate mice carrying mutations in α-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-/0FvQ/Q + Gla-/- FvQ/Q) vs. (Gla-/0Fv+/+ ) = (0.28±0.03)% vs. (0. 07±0. 007)%, P<0. 01, (Gla /0 FvQ/Q + Gla-/- FvQ/Q) vs. (Gla+/0 FvQ/Q + Gla+/+FvQ/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-/-FvQ/Q + Gla-/-FvQ/Q) vs. (Gla /0Fv+/+) = 1. 9 + 0. 7 vs. 0.0 + 0.0, P< 0.05, (Gla /0FvQ/Q + Gla-/-FvQ/Q) vs. (Gla+/0FvQ/Q + Gla+/+FvQ/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.
