局部联合应用反义核酸对大鼠颈动脉肌内膜增殖的作用

Effects of Locally Delivered Antisense Oligonucleotides on Myointimal Hyperplasia of Rat Carotid Artery after Nitrogen Drying

目的：观察局部联合应用反义ｃｍｙｂ 、反义ｃＨａｒａｓ 对氮气干燥内皮剥脱术后大鼠颈动脉肌内膜增殖的抑制作用。方法：５０ 只ＳＤ 大鼠随机分为对照组、错配组、反义ｃｍｙｂ 组、反义ｃＨａｒａｓ 组和联合用药组，于内皮剥脱后经凝胶球囊局部导入不同核酸片段。术后１４ 天取材制片，采用计算机图像分析法测量管腔面积，内／ 中膜面积、厚度比值。结果：联合用药组管腔面积（０－３９ ±０－１２ ｍ ｍ２） 大于反义ｃｍｙｂ 、反义ｃＨａｒａｓ 组（０－２９ ±０－０１ ｍ ｍ ２ ，０－２８ ±０－０１ ｍ ｍ２ ，Ｐ＜ ０－０５） 和错配组（０－１８ ±０－０５ ｍ ｍ ２ ，Ｐ＜ ０－０１） ，与对照组（０－４０ ±０－１４ ｍ ｍ２） 比较，管腔面积无显著差异（ Ｐ＞ ０－０５） 。其内／ 中膜面积、厚度比值（０－１１ ±０－０２ ，０－０２ ±０－００） 均低于单一制剂组和错配组（０－４５ ±０－２４ ，０－３９ ±０－２５ ；０－５７ ±０－２４ ，０－５６ ±０－２３ ；１－１６ ±０－３８ ，１－８５ ±０－７９ ；Ｐ＜０－０１） 。结论：局部靶向联合应用反义ｃｍｙｂ 、反义ｃＨａｒａｓ 能进一步抑制血管损伤后肌内膜增殖。

Objective: To determine if antisense c myb plus c Ha ras delivered locally via hydrogel catheter inhibits the development of myointimal hyperplasia in rat carotid artery after nitrogen desiccation of the endothelium Methods: Fifty SD rats were randomized into five groups (ten in each) After endothelial injury, different antisense oligonucleotides were administered locally through hydrogel catheter Animals were killed 14 days after gas drying The lumen areas, ratios of intimal to medial area and intimal to medial thickness were measured with the aid of computer The q test was used for statistical analysis Results: The lumen area of the combined (antisense c myb and c Ha ras) group (0 39±0 12 mm 2) was larger than that of the antisense c myb , c Ha ras and mismatch mismatching oligonucleotide) groups (0 29±0 01 mm 2, q =3 488 2; 0 28±0 01 mm 2, q =3 744 1; p <0 05; 0 18±0 05 mm 2, q =7 064 0, p <0 01, respectively) No difference in lumen areas was found between the combined group and control group (0 40±0 14 mm 2, q =0 117 8, p >0 05) The ratios of intimal to medial area and intimal to medial thickness for the combined group (0 11±0 02, 0 02±0 00) were significantly decreased compared with the antisense c myb、 c Ha ras and mismatch groups (0 45±0 24, 0 39±0 25 and 1 16±0 38; q =9 871 7, 9 545 2 and 30 682 2; 0 57±0 24, 0 56±0 23 and 1 85±0 79; q =9 144 2, 8 847 7 and 29 564 7, respectively; p <0 01) Conclusion: Myointimal hyperplasia of rat carotid artery after nitrogen drying can be further suppressed by local intravascular delivery of combined antisense c myb and c Ha ras The technique is promising to be used to prevent injured artery from obstructive stenosis