摘要
选用高效选择性 i NOS抑制剂 1 4 0 0 w治疗 96只雄性大鼠提睾肌缺血再灌注损伤 ,观测去神经完全缺血 3小时大鼠提睾肌再灌注 90分钟期间滋养动脉血管管径恢复率及血液流动率变化 ,探讨选择性抑制i NOS对骨骼肌缺血再灌注损伤的治疗作用及机制。结果发现 ,大鼠提睾肌去滋养神经后完全缺血 3小时 ,随着血循环的重建 ,PBS组“无复流”现象的发生率为 2 0 % ,70 %的实验动物在灌注半小时内血管管径及血流恢复率仅为缺血前的 60～ 80 % ;而 1 4 0 0 W组 ,“无复流”现象降低至 5% ,90 %的实验动物在灌注 1 0分钟后血管管径及血流速率均增至缺血前的 1 1 0～ 1 2 0 % ,肌肉表面光洁度基本正常。此外 ,注射 PBS与 1 4 0 0 W后 ,连续测量大鼠的血压、呼吸、脉搏三大生命体征 2小时 ,生命体征平稳。从而表明 ,1 4 0 0 W通过选择性高效抑制 i N-OS,能够减轻或消除骨骼肌缺血再灌注损伤 。
Objective:This study was designed to observe the effects of a selective inducible NO synthase (iNOS) inhibitor on microcirculation of denervated I/R skeletal muscle that is more relevant to the clinical practice.Methods:The left cremaster muscles of 96 male rats, which were randomly divided into two groups,and its pudic-epigastric artery, vein and the genito- femoral nerve were isolated. Three hours of ischemia was achieved by clamping the main vascular pedicle of the isolated muscle and denervation by resecting a 3 mm segment of the genitofemoral nerve. Rats in the experimental group subcutaneously received selective iNOS inhibitor dihydrochloride (1400W, 0.1mg/100g) at 10 min prior to reperfusion.Rats in the control group received the same volume of phosphate buffering saline (PBS). For each group, vessel diameter changes in a selected arterial tree containing vessel sizes of 10-70um during reperfusion were measured by an intravital microscope that connected to a recording and measuring system. Overall blood flow of the muscle was measured by laser Doppler flowmetry.Results:At 10 min of reperfusion, the mean blood flow was 30.2% of baseline in the control group and 76.3% in the 1400W-treated group (p<0.01). The blood flow gradually increased to 67.5% in the control group at 60 min. In the 1400W-treated group, the mean blood flow reached its maximum of 106.0% at 50 min of reperfusion. The average diameters of the selected arteries inthe controls were between 57% and 68% of baseline at 10 min of reperfusion and gradually increased to the maximum level of 78.0% at 90 min of reperfusion. In contrast, the diameter in the 1400W-trated group sharply increased to 118% at 10 min of reperfusion and remained at 127 to 148% throughout 90 min of observation.Conclusion:(1) The treatment with 1400W remarkably magnified blood flow and increased vessel diameter in the denervateimpd cremaster muscle during early reperfusion following 3 hrs of warm ischemia, improved microcirculation in the reperfused tissue, and reduced reperfusion injury and eliminated the 'no-reflow' phenomenon. (2) Inhibition of iNOS by dihydrochloride is independent of innervation.
出处
《中国中医骨伤科杂志》
CAS
2000年第6期10-15,共6页
Chinese Journal of Traditional Medical Traumatology & Orthopedics
基金
博士论文
