抑制大鼠动脉损伤后早期中膜平滑肌细胞增殖可降低内膜肥厚

目的:探讨早期中膜平滑肌细胞增殖与内膜肥厚的关系。方法:球囊导管损伤大鼠动脉后,在不同时期投予血管紧张素转换酶抑制剂(ACEI)(temocapril-HCl,10mg·kg^-1·d^-1),观察平滑肌细胞BrdU(5-溴脱氧尿嘧啶尿苷)标记率和内膜面积。结果:损伤后动脉中膜平滑肌BrdU阳性细胞出现于术后24h,BrdU标记率呈双峰期变化,第1期在1-3d,峰值在2d为5.3%,第2期在3-7d,峰值在5d为2.7%。在第1个增殖期投予temocapril显著抑制第2个增殖期的BrdU标记率(0.05±0.02)%,对照组为(4.50±0.27)%(P＜0.01),同时也显著抑制了术后10d内膜面积的增加(10670.1μm²±7713.3μm²)(P＜0.01)。而仅在第2个增殖期投药,则不能抑制内膜面积的增加(83499.5μm²±31360.0μm²)(P＞0.05),其程度与未投药组相当。结论:球囊导管损伤后动脉中膜平滑肌细胞第1个增殖期是内膜形成所必需的。

Reduction of intimal thickening by inhibition of early rat medial smooth muscle cell proliferation induced by arterial injury

AIM:To investigate the relationship between medial smooth muscle cell proliferation and intimal thickening.METHODS:Angiotensin converting enzyme inhibitor (temocapril-HCl, 10 mg·kg^-1·d^-1) was administered in various periods after rat arterial injury by balloon catheters. The labeling BrdU indexes of smooth muscle cell and intimal areas were observed. RESULTS:Positive medial smooth muscle cells for BrdU occurred at 24 hours after injury. The labeling indexes for BrdU showed biphasic change, the period of the first peak appeared within day 1-3, the peak value was 5.3% at 2 days. The period of the second peak appeared within day 3-7, the peak was 2.7% at 5 days. Administration of temocapril in the first proliferation phase significantly suppressed the labeling BrdU index(0.05±0.02)%vs (4.50±0.27)%,P＜0.01 in the second one, also the intimal area at 10 days . Administration of temocapril in the second phase, however, did not effectively suppress the intimal formation which was approximate to the vehicle-treated group(P＞0.05). CONCLUSION:The first proliferative phase of arterial medial smooth muscle cell after balloon injury is necessary to the intimal formation.