Effects of Endovascular Brachytherapy with ^(192)Ir Afterloading System on Expression of Type I Collagen after Angioplasty

Objectives To investigate the effect and mechanism of endovascular brachytherapy with 192Ir on expression of type I colla gen, metalloproteinases - 1 (MMP - 1) and the tissue inhibitor (TIMP - 1 ) after angioplasty. Methods Restenotic model of domestic microswine was employed and the iliac arteries were randomized to radiation group (n = 12), which were treated with 20 - 25 Gy of 192Ir, and non - radiation group ( n = 36) after angioplasty. The target vessels were harvested in the end of 3 months and 6 months after angioplasty. Im-munohistochemistry and in situ hybridization were used to detect proteins of type I collagen, MMP - 1 and TIMP -1, and mRNA expression of type I collagen. Results The protein and mRNA of type I collagen, the ratios of TIMP-1/MMP-1 were significantly lower in radiation group than in non - radiation group (P < 0. 05 or 0. 01). The peak of transcription of type I collagen mRNA was at 6 months and 3 months in non - radiation group and radiation group respectively. Conclusions Endovascular brachytherapy with 192Ir might modify the metabolism of extracellular matrix after angioplasty by inhibiting the synthesis of type I collagen and the activities of MMP - 1 and TIMP - 1.

兔髂动脉球囊成形及支架术后血管壁超微结构的观察

目的 :比较兔髂动脉球囊成形及支架术后血管壁超微结构的变化 ,探讨支架内再狭窄与球囊血管成形术后再狭窄的不同机制。方法 :10支兔 ,分别于左髂动脉行 NIR支架置入术 (S组 ) ,右髂动脉行球囊成形术 (B组 )。术前3d始予阿司匹林 2 5 mg· d- 1 ,直至处死动物。术后皮下注射肝素 2 5 0 0 U· d- 1 ,连续 7d。术后 7d和 30 d处死动物。用光镜、透射电镜及免疫组化染色技术观察损伤部位血管壁变化。结果 :术后 30 d光镜检查发现 S组新生内膜平滑肌细胞 (SMC)的增生程度明显高于 B组 (P<0 .0 5 )。电镜检查 ,术后 7d,S组较 B组可见较多从外膜向中膜及内膜迁移的肌纤维母细胞 ,中膜及内膜大量以合成型为主的 SMC,细胞外基质 (ECM)以胶原及弹性纤维为主。30 d时 B组内膜下 SMC已转化为收缩型 ,ECM以胶原及弹性纤维为主 ;而 S组内膜下大量 SMC仍为典型合成型表现 ,周围 ECM以氨基聚糖及糖蛋白为主。结论 :球囊成形术及支架术后 ,新生内膜组成成分不同 ,支架术后新生内膜增生以 SMC增生为主 ,ECM以氨基聚糖及糖蛋白为主而球囊成形术后新生内膜增生 SMC较少 。

MMP_2和MMP_9在损伤血管中的原位表达

目的探讨基质金属蛋白酶在血管损伤后的改变及可能作用。方法在大鼠胸主动脉球囊损伤的模型上，应用原位杂交的方法，观察了MMP2、MMP9在血管损伤后不同时间的表达情况。结果MMP2在球囊损伤后第三天开始表达，第7天达高峰，第14天未见表达，MMP9从第3天开始表达，并一直持续到14天，但第14天只有新生内膜部位有少量表达。结论MMP2、MMP9在血管损伤后，异常表达，可能与平滑肌细胞迁移、新生内膜形成及血管重塑有关。

碱性成纤维细胞生长因子对大鼠血管球囊成形术后基质金属蛋白酶表达的影响

目的：探讨碱性成纤维细胞生长因子对基质金属蛋白酶表达的影响及其在球囊术后再狭窄中的作用。方法：２４只雄性Ｗｉｓｔａｒ大鼠分成对照组、球囊损伤组（１４ｄ）及实验组。正常组不做处理；球囊损伤组行单纯球囊拉伤，术后１４ｄ取材；实验组大鼠胸主动脉球囊成形，术后即刻、３、６、９ｄ分别尾静脉注射１０、５、３、２μｇ碱性成纤维细胞生长因子，１４ｄ处死取材，Ｎｏｒｔｈｅｒｎ杂交观察基质金属蛋白酶１、２及９的ｍＲＮＡ的改变。结果：正常对照组，基质金属蛋白酶１、２及９均无明显表达。球囊损伤组，只有基质金属蛋白酶９有较少量表达；实验组基质金属蛋白酶１明显表达，基质金属蛋白酶９表达较球囊损伤组升高，基质金属蛋白酶２仍无明显表达。结论：碱性成纤维细胞生长因子能选择性促进成形术后基质金属蛋白酶的表达，可能在调节细胞外基质的降解。