摘要
目的:观察腹主动脉局部动脉壁剪切力增高对腹主动脉管径及管壁MMP-9表达的影响,并分析剪切力增高在动脉重塑中的作用。
方法:S-D大鼠48只,随机分8组,每组6只,4组为实验组,4组为对照组。实验组行肾动脉下腹主动脉-下腔静脉细针穿刺造瘘,对照组除不造瘘外,各项操作同实验组。分别于术后1天,7天,14天,28天取标本,并分别在术后即时和取标本时测瘘口近端动脉外径,免疫组化及IPP图像分析技术观察MMP-9动态表达及瘘口近端动脉内径周长,管壁厚度的改变。
结果:术后即时,瘘口近端动脉管径稍有扩张,但与术前无明显差异,术后第1天,瘘口近端动脉管径明显增大(P<0.05),扩张率达19%,管壁变薄(P<0.05),并随时间增加,管径不断增大,管壁不断变薄,到术后28天,动脉管径几乎达到未造瘘时的2倍;部分动脉扭曲明显;内皮细胞结构逐渐紊乱,内弹力层崩解,管壁大量炎性细胞浸润,中膜平滑肌结构进行性紊乱;MMP-9于术后1天开始表达,术后7天达高峰(P<0.01),并持续高表达(P<0.01)。
结论:1.剪切力增高可使局部动脉出现管径增大,管壁变薄的正性重塑;2.剪切力增高导致管壁MMP-9表达上调;3.动脉管径增大及管壁变薄与MMP-9表达增高密切相关;4.剪切力增高,MMP-9表达增多是导致动脉瘤形成后逐渐增大及动静脉瘘形成后瘘口近远端逐渐膨大的主要因素。
Objective: To observe the expression of MMP-9 and the arterial caliber change in conditions that local arterial wall sheer stress is elevated and analyse the relationship between high shear stress and arterial remodling.
Methods: 48 S-D rats were divided into 4 experiment and 4 comparison groups averagely at radom, During the operation of the experiment groups, An infra-renal aortocaval fistula was construsted by needle puncture using a 22-G needle.The aorta proximal to the fistula was harvested after 1 day,7 days, 14 days and 28 days respectively,while sham operations were done in the comparison groups.The diameters of the aorta were measured after fistula made and before harvest.The internal perimeter and wall thickness were measured by computer skills.The level change of MMP-9 was observed by immunohistochemistry and computer skills.
Results: The diameters and the internal perimeters were enlarged in the 1day group at the sacrifice time (p<0.05),and the value was growing with the time ;Meanwhile, wall thickness were decreased with the time. Large amount of inflammatory cells soakaged the hemal wall,and endothelial cells and internal elastic lamina were destructed with the time,Stastics of all the result showed that MMP-9 had reached the peak value in the 7days group(p<0.01) ,and remained a high level expression continually.
Conclusions: when shear stress increases, the diameters of arteries increase by company of wall thickness decrease; the expression of MMP-9 up-regulates and gets a top in 7 day after operation ;the enlargement of the aorta and the decrease of wall thickness has a close relationship with the continuous expression of the MMP-9;and MMP-9 may be involved in the flow induced arterial remodling.
引文
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