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细胞因子治疗动脉再狭窄:γ-干扰素抑制内膜增生

Cytokine therapy for arterial restenosis: inhibition of neointimal hyperplasia by gamma-interferon.

作者信息

Castronuovo J J, Guss S B, Mysh D, Sawhney A, Wolff M, Gown A M

机构信息

Department of Surgery, Morristown Memorial Hospital, New Jersey 07962-1956, USA.

出版信息

Cardiovasc Surg. 1995 Oct;3(5):463-8. doi: 10.1016/0967-2109(95)94442-y.

DOI:10.1016/0967-2109(95)94442-y
PMID:8574526
Abstract

Inhibition of neointimal hyperplasia by gamma-interferon (gIFN) treatment was evaluated. Four groups of Sprague-Dawley rats (n = 72) weighing 500 g underwent endothelial injury of the carotid artery using the previously described Fogarty catheter technique. Group I (controls, n = 8) received one phosphate-buffered saline (PBS) injection 24h before injury and every 24h thereafter for a total of eight injections. Groups II (n = 8) and III (n = 8) received daily injections of 200,000 units of gIFN according to the same schedule except that group III did not receive the preoperative dose. Animals were killed on postoperative day 14. Histologic sections were analyzed morphometrically and immunohistochemically. Both gIFN groups had a statistically significant 50% reduction of the cross-sectional area of the neointimal hyperplasia compared with that of the controls (P < 0.01). Cell replication analysis of smooth muscle cells in the media and neointima revealed no statistically significant difference between controls and gIFN-treated groups. Group IV consisted of 48 rats that were treated with either PBS or gIFN on a schedule similar to that of groups I and II. Animals were killed at frequent time intervals during the first 7 days after injury. Their arteries were analyzed histologically and immunohistochemically. The results confirm previous findings that gIFN reduces the development of neointimal hyperplasia following arterial injury. The results also indicate that smooth muscle cells restore their proliferative activity by 7 days after discontinuation of gIFN treatment. It is proposed that efficacy of gIFN can be enhanced by lengthening the period of treatment.

摘要

评估了γ-干扰素(gIFN)治疗对新生内膜增生的抑制作用。四组体重500g的Sprague-Dawley大鼠(n = 72)采用前述Fogarty导管技术对颈动脉进行内皮损伤。第一组(对照组,n = 8)在损伤前24小时接受一次磷酸盐缓冲盐水(PBS)注射,此后每24小时注射一次,共注射八次。第二组(n = 8)和第三组(n = 8)按照相同的时间表每天注射200,000单位的gIFN,不同之处在于第三组未接受术前剂量。术后第14天处死动物。对组织学切片进行形态计量学和免疫组织化学分析。与对照组相比,两个gIFN组的新生内膜增生横截面积均有统计学意义的50%降低(P < 0.01)。对中膜和内膜平滑肌细胞的细胞增殖分析显示,对照组和gIFN治疗组之间无统计学显著差异。第四组由48只大鼠组成,按照与第一组和第二组相似的时间表用PBS或gIFN治疗。在损伤后的前7天内,每隔一段时间处死动物。对其动脉进行组织学和免疫组织化学分析。结果证实了先前的发现,即gIFN可减少动脉损伤后新生内膜增生的发展。结果还表明,在停止gIFN治疗后7天,平滑肌细胞恢复其增殖活性。有人提出,延长治疗时间可提高gIFN的疗效。

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