1.3.4　血管分叉处的低密度脂蛋白浓度分布

血管几何形状变化引起的流场变化会显著影响LDL浓度分布。先前的研究表明，流场扰动发生在分叉血管段。为了支持这一假设，将DiI-LDL注射到Flk1：GFP胚胎中，血液在48 h.p.f循环，LSCM在52 h.p.f观察到LDL荧光分布。红色荧光强度的定量测量表明，分叉腔表面的LDL浓度明显高于平直表面的LDL浓度（图1-13）。

在72 h.p.f，在尾静脉中观察到明显的脂质沉积（图1-14）。在同一部位，LDL渗入内皮下（图1-14，箭头）。

我们的实验表明斑马鱼胚胎尾静脉中发生脂质沉积，并且LDL渗透到尾静脉的内皮下层。在斑马鱼的胚胎阶段，大动脉和静脉直接连接，而不是通过毛细管网络间接连接，静脉中脂质沉积与血管几何形状的急剧改变密切相关。在成年斑马鱼中，仅在背主动脉中发现病变，而在尾静脉中未发现病变。为什么AS性病变仅发生在动脉？我们认为，动脉是高压系统，因此脂质可以更容易地穿透血管壁。其次，由于动脉壁很厚，脂质很容易在动脉壁中被阻滞，不容易从壁中渗透出来，也不容易被淋巴系统排出。而静脉壁是很薄的低压系统，脂质很容易从静脉壁渗出，并容易被淋巴系统排出。

图1-12　血管系统中的LDL浓度极化。（a）Flk1：52 h.p.f.的GFP胚胎；（i — iii）在48 h.p.f注射DiI-LDL的胚胎。血管内皮细胞为绿色，DiI-LDL为红色。（b）静脉和（c）动脉的红色荧光强度。编号1至5表示样品在血管中的位置［图1-12（a）中的ii、iv、vi］：1和5是血管的内膜表面；从2到4表示血管内膜到血管中心。3是血管中心（*p＜0.05; **p＜0.01）。［引自：Xie X, et al. In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish［J］. J R Soc Interface, 2013, 10（82）: 20121053.］
Figure 1-12　LDL concentration polarization in the vascular system. （a）Flk1: 52 h.p.f. GFP embryos; （i — iii）48 h.p.f. DiI-LDL embryos. The endothelial cells were green and DiI-LDL was red. Red fluorescence intensity of vein （b） and artery （c）. Numbers 1 to 5 indicated the position of the sample in the vessel ［Fig. 1-12（a）ii、iv、v］: 1 and 5 presented the lumen surface of the vessel; 2 to 4 presented from the lumen surface to the vessel center. 3 presented the vascular center （*p＜0.05; **p＜0.01）. ［Adapted from: Xie X, et al. In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish［J］. J R Soc Interface, 2013, 10（82）: 20121053.）(https://www.daowen.com)

图1-13　分叉处血管腔表面的LDL浓度显著高于直段。（a）Flk1：52 h.p.f.的GFP胚胎； 内皮细胞为绿色，DiI-LDL为红色。（b）红色荧光强度的统计分析。**p＜0.01。［引自：Xie X, et al. In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish［J］. J R Soc Interface, 2013, 10（82）: 20121053.］
Figure 1-13　The concentration of LDL on the surface of the vessel lumen at the bifurcation point is significantly higher than that in the straight section. （a）Flk1: 52 h.p.f. GFP embryo; endothelial cells were green, DiI-LDL was red. （b）Statistical analysis of red fluorescence intensity. **p＜0.01. ［Adapted from: Xie X, et al. In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish［J］. J R Soc Interface, 2013, 10（82）: 20121053.］

图1-14　LDL在血管系统中的积累和渗透。（a）—（c）Flk1：72 h.p.f.的GFP胚胎，内皮细胞为绿色，Dil-LDL为红色。箭头表示LDL渗透的位置。［引自：Xie X, et al. In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish［J］. J R Soc Interface, 2013, 10（82）: 20121053.］
Figure 1-14　The accumulation and penetration of LDL in the vascular system. （a）—（c）Flk1: GFP embryos at 72 h.p.f.; The endothelial cells were green and DiI-LDL was red. The arrow indicates the location of LDL penetration. ［Adapted from: Xie X, et al. In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish［J］. J R Soc Interface, 2013, 10（82）: 20121053.］