Rho激酶抑制剂对移植静脉内膜影响的实验研究  

EXPERIMENTAL STUDY ON Rho-KINASE INHIBITOR BY INTRAVENOUS INJECTION INHIBITING INTIMAL HYPERPLASIA IN VEIN GRAFTS

作　　者：郑占乐[1] 潘进社[1] 马利杰[1] 于贤[2] 郭明珂[1] 姚双权[1] 

机构地区：[1]河北医科大学第三医院创伤急救中心,石家庄050051 [2]河北省人民医院内分泌科

出　　处：《中国修复重建外科杂志》2009年第9期1110-1113,共4页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：河北省自然科学基金资助项目(C2008000926)~~

摘　　要：目的探讨Rho激酶抑制剂——盐酸法舒地尔对兔动脉损伤后移植静脉内膜增厚的影响。方法健康新西兰白兔24只,体重2.3～2.5kg,随机分为实验组和对照组(n=12)。实验组术前3d每天静脉滴注盐酸法舒地尔(30mg/kg)至取材,对照组静脉滴注等量生理盐水作为空白对照。术中游离实验动物股动、静脉各3cm,切除股动脉1cm造成缺损,取2.5cm股静脉倒置后端端吻合于动脉缺损处。术后观察动物一般情况,于2、4周时取移植静脉行组织学、免疫组织化学、凋亡细胞检测和透射电镜观察,测定内膜厚度、平滑肌细胞增殖与凋亡细胞比率。结果术中及术后无动物死亡,伤口愈合良好。术后3d和取材前彩色超声多普勒检查示移植静脉均通畅。组织学观察术后2、4周两组移植静脉内膜均增厚,内膜区细胞增多,中膜平滑肌细胞增生并呈梭形。术后2、4周,实验组及对照组血管内膜厚度分别为(30.33±3.23)、(43.11±4.92)μm和(44.83±3.53)、(66.16±8.45)μm;增殖性细胞核抗原阳性细胞比率分别为14.28%±2.76%、7.61%±1.06%和20.08%±3.56%、8.73%±1.35%;TUNEL阳性细胞比率分别为3.55%±0.36%、1.22%±0.18%和1.11%±0.31%、0.55%±0.11%;以上指标各时间点组间比较以及组内各时间点比较差异均有统计学意义(P<0.05)。结论静脉滴注盐酸法舒地尔可有效抑制兔动脉损伤后移植静脉内膜增厚。Objective To investigate the effects of Rho-kinase inhibitor - fasudil hydrochloride hydrate on vein graft intimal hyperplasia in vivo. Methods Twenty-four healthy rabbits （2.3-2.5 kg） were randomly divided into two groups （n=12）. Fasudil hydrochloride hydrate （experimental group） and normal sodium （control group） were given 3 days before operation with 30 mg/kg by intravenous injection everyday and continued until the end of the experiment. After a longitudinal incision, the femoral vein and the famoral artery were exposed about 3 cm. An approximately 2.5 cm segment of the famoral vein was harvested for the reversed-vein graft. The femoral artery was removed 1 cm segment and replaced by the harvested femoral vein. At 2 and 4 weeks after operation, the grafts were stained with HE to observe the thickness of the intima. Furthermore, the proliferating cell nuclear antigen （PCNA） and transmission electron microscope was used to study the proliferation of smooth muscle cell. In situ apoptosis was detected by TUNEL assay. Results All rabbits survived till the end of the experiment. The color Doppler imaging examination showed that all grafts were patency. At 2 and 4 weeks after the operation, HE staining showed that the intimal hyperplasia were obvious in the two groups. There were lots of Cells in the intima, and more fusiform smooth muscle cells in the media. At 2 and 4 weeks, the intimal thickness were （30.33 ± 3.23） μm and （43.11 ± 4.92） μm in experimental group and were （44.83 ± 3.53） μm and （66.16 ± 8.45） μm in control group. The rates of PCNA positive cell were 14,28% ± 2,76% and 7.61% ± 1.06% in experimental group and were 20.08% ± 3.56% and 8.73% ± 1.35% in control group. The rates of TUNEL positive cell were 3.55% ± 0.36% and 1.22% ± 0.18% in experimental group and were 1.11% ± 0.31% and 0.55% ± 0.11% in control group. There were significant differences （P 〈 0.05） between the two groups at 2 weeks or 4 weeks, between 2 weeks and 4 weeks within group.

关 键 词：RHO激酶抑制剂 盐酸法舒地尔 静脉移植 内膜增厚 兔 

分 类 号：R654.3[医药卫生—外科学]