局部递送c-myc反义寡核苷酸联合188Re液体填充球囊血管内近距离放射治疗对兔髂动脉球囊导管损伤后血管平滑肌细胞增殖的影响。

The effect of locally delivered c-myc antisense oligonucleotides combined with intravascular brachytherapy of 188Re liquid-filled balloon therapy on vascular smooth muscle cell proliferation in rabbit iliac arteries after injury with a balloon catheter.

作者信息

Wang Wei, Li Ji-Lin, Wang Xin

机构信息

Cardiovascular Department of 1st Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong province 515041, China.

出版信息

Biochem Cell Biol. 2007 Apr;85(2):164-8. doi: 10.1139/o06-206.

DOI:10.1139/o06-206

PMID:17534395

Abstract

Poststenting restenosis is a significant clinical problem that involves vascular smooth muscle cell (VSMC) proliferation. We primarily investigated the effect of c-myc antisense oligodeoxynucleotides (ASODNs) combined with 188Re radiation therapy on VSMC proliferation in rabbit common iliac arteries injured by the porous balloon catheter to explore the therapeutic potential of the combined therapy for the prevention of restenosis. The iliac arteries in rabbits were injured with balloon catheters, and radiation therapy was carried out with a 2.5 mm balloon catheter filled with 188Re (8 or 15 Gy), and ASODNs (300 microg) were applied to the adventitia introduced using a pluronic gel releasing system and a lipofectin delivery system. After 3 weeks, the animals were killed and defined segments of arteries were sectioned. The histological sections were stained using alpha-actin immunohistochemistry staining. The positive alpha-actin ratios were calculated and analyzed statistically among groups. In contrast to the rate of alpha-actin positive cell staining in the control group, the rate of alpha-actin positive cell staining did not decrease (P > 0.05) in the 188Re-irradiated group (8 Gy). However, in the ASODN-treated group, the 188Re-irradiated group (15 Gy), and the combined ASODN - 188Reirradiated groups (8 or 15 Gy), the ratios had markedly decreased (P < 0.01). The effect of the combined group (ASODNs + 188Re (15 Gy)) provided the lowest level of alpha-actin positive cell staining (P < 0.01). The ASODNs (300 microg) effectively decreased VSMC poliferation. The effect of the 188Re radiation on the VSMCs depended on the dosage. The ASODNs (300 microg) and combined 188Re irradiation effectively lowered VSMC proliferation, and the effect was better than that achieved with any other treatment.

摘要

支架置入术后再狭窄是一个涉及血管平滑肌细胞（VSMC）增殖的重大临床问题。我们主要研究了c-myc反义寡脱氧核苷酸（ASODNs）联合188Re放射治疗对经多孔球囊导管损伤的兔髂总动脉中VSMC增殖的影响，以探索联合治疗预防再狭窄的治疗潜力。用球囊导管损伤兔的髂动脉，用填充有188Re（8或15 Gy）的2.5 mm球囊导管进行放射治疗，并使用普朗尼克凝胶释放系统和脂质体递送系统将ASODNs（300μg）应用于外膜。3周后，处死动物并将确定的动脉段切片。组织学切片用α-肌动蛋白免疫组织化学染色。计算α-肌动蛋白阳性率并在组间进行统计学分析。与对照组α-肌动蛋白阳性细胞染色率相比，188Re照射组（8 Gy）α-肌动蛋白阳性细胞染色率未降低（P>0.05）。然而，在ASODN治疗组、188Re照射组（15 Gy）以及ASODN与188Re联合照射组（8或15 Gy）中，该比率显著降低（P<0.01）。联合组（ASODNs + 188Re（15 Gy））的效果使α-肌动蛋白阳性细胞染色水平最低（P<0.01）。ASODNs（300μg）有效降低了VSMC增殖。188Re对VSMCs的作用取决于剂量。ASODNs（300μg）与188Re联合照射有效降低了VSMC增殖，且效果优于其他任何治疗方法。