Stucker O, Bonhomme E, Lenaers A, Teisseire B
Groupe de Recherches Servier, Societé Fondax, Puteaux, France.
Int Angiol. 1989 Oct-Dec;8(4 Suppl):39-43.
We studied the in vivo effects of Daflon 500 mg on transvascular movement of macromolecules induced by bradykinin (BK) and ischemia. The experimental preparation involved the rat cremaster muscle. The muscle was fashioned as a single bag (new procedure), placed in a transparent chamber and superfused with a bicarbonate buffer solution equilibrated with a 5% CO2 95% N2 gas mixture in order to obtain pH 7.40, PCO2 = 40 mmHg, PO2 = 20-40 mmHg and thermostated at 35 degrees C. FITC-Dextran 150 (MW 150,000) was injected i.v. as a macromolecular tracer. BK was added to the buffer solution at the concentration of 2 micrograms/ml five minutes after a control period of 60 minutes. Ischemia was performed during 60 min by a clamp positioned on the main artery of the cremaster muscle. Animals treated with Daflon 500 mg (100 mg/kg) 18 and 2 hours before experiments showed a significant reduction in FITC-Dextran 150 leakage in both BK and ischemia protocols. Leakage of FITC-Dextran 150 started 2-3 min after application of BK in the two animal groups but the response was less important (+ 270%) and the preparation returned to control appearance after 40 min in the treated rats in contrast with control rats (+ 450% and 70 min). The amplitude of FITC-Dextran 150 leakage was identical just one hour after ischemia in the two animal groups, but microvascular permeability returned to basal state in treated animals (30 min), a fact non observed in non treated animals. These data demonstrate the protective effect of Daflon 500 mg on the microvascular muscle network in vivo.
我们研究了500毫克屈黄酮对缓激肽(BK)和缺血诱导的大分子跨血管运动的体内效应。实验采用大鼠提睾肌。将肌肉制成单个囊袋(新方法),置于透明腔室中,并用与5%二氧化碳-95%氮气混合气体平衡的碳酸氢盐缓冲溶液进行灌流,以达到pH 7.40、PCO2 = 40 mmHg、PO2 = 20 - 40 mmHg,并在35摄氏度恒温。静脉注射异硫氰酸荧光素标记的葡聚糖150(分子量150,000)作为大分子示踪剂。在60分钟的对照期后,将BK以2微克/毫升的浓度加入缓冲溶液中。通过夹闭提睾肌的主要动脉进行60分钟的缺血处理。在实验前18小时和2小时给予500毫克屈黄酮(100毫克/千克)治疗的动物,在BK和缺血方案中,异硫氰酸荧光素标记的葡聚糖150渗漏均显著减少。在两个动物组中,应用BK后2 - 3分钟开始出现异硫氰酸荧光素标记的葡聚糖150渗漏,但与对照大鼠(增加450%,持续70分钟)相比,治疗组大鼠的反应较小(增加270%),且在40分钟后制剂恢复到对照外观。在两个动物组中,缺血1小时后异硫氰酸荧光素标记的葡聚糖150渗漏幅度相同,但治疗组动物的微血管通透性在30分钟后恢复到基础状态,这在未治疗的动物中未观察到。这些数据证明了500毫克屈黄酮对体内微血管肌肉网络的保护作用。