细胞钙离子转运蛋白兰尼碱受体3与ApoE基因敲除小鼠动脉粥样硬化斑块形成的关系

目的:观察细胞钙离子转运蛋白兰尼碱受体3(ryanodine receptor 3, RYR3)在动脉粥样硬化斑块形成过程中的改变,探讨两者的相关性。方法:选取6周龄雄性载脂蛋白E基因敲除(ApoE^-/-)小鼠及野生型C57BL/6J小鼠,高脂饲喂20、27和33周后,在各个时点处死动物取主动脉根部制作连续切片。(1)HE染色,观察组织形态学的变化,计算机图像分析仪测量斑块面积和血管管腔面积,计算校正斑块面积(斑块面积/血管管腔面积)。(2)免疫组织化学染色,计算机图像分析仪测定不同周龄小鼠细胞钙离子转运蛋白RYR3表达变化。结果:与同周龄对照组小鼠相比,ApoE^-/-小鼠体内RYR3表达显著减少(P<0.05),随着ApoE^-/-小鼠周龄的增加,RYR3的表达明显减少,且与斑块面积/血管管腔面积呈负相关(r＝-0.652,P<0.01)。结论:细胞钙离子转运蛋白RYR3参与动脉粥样硬化的病理过程,且与动脉粥样硬化斑块的形成密切相关。

Relationship between cell calcium ion transporter ryanodine receptor 3 and atherosclerotic plaque in apolipoprotein E gene-deficient mice

AIM:To investigate the change of cell calcium ion transporter ryanodine receptor 3(RYR3) in the aorta smooth muscle cells of apolipoprotein E gene-deficient(ApoE^-/-) mice, and to elucidate the relationship between RYR3 and atherosclerotic plaque in ApoE^-/- mice. METHODS:Six-week-old ApoE^-/- mice and wild-type C57BL/6J mice were used in the experiment. The animals were sacrificed for pathological observation at the time points of 20, 27 and 33 weeks after hyperlipidic diet, respectively. Four sections of the aortic root were prepared and HE and immunohistochemical staining were performed. All the sections were analyzed with a computer image analysis system. RESULTS:Compared with the controls, the expression of RYR3 was markedly lower in ApoE^-/- mice(P<0.05). As the age of ApoE^-/- mice increasing, the expression of RYR3 decreased significantly, and was negatively correlated to the plaque area corrected by lumen area(r＝-0.652, P<0.01). CONCLUSION:Cell calcium ion transporter RYR3 participates in the pathological process of atherosclerosis, and is closely related to the formation of atherosclerotic plaques.