复方甘草酸苷对兔骨骼肌缺血再灌注损伤的影响

Effect of compound glycyrrhizin on ischemia/reperfusion injury in the skeletal muscle of rabbits

背景:甘草酸苷对缺血再灌注损伤保护作用的研究主要集中于心、肾、肠等器官,对骨骼肌的研究甚少。目的:验证复方甘草酸苷对兔骨骼肌缺血再灌注损伤的保护作用。设计、时间及地点:血清学及组织形态学水平的随机对照动物实验,于2008-02/09在重庆医科大学临床检验诊断学教育部重点实验室完成。材料:选用24只新西兰大白兔,按随机数字表法分为3组,即假手术组、模型组及复方甘草酸苷组,每组8只。方法:模型组动物制备右后肢骨骼肌缺血损伤模型,缺血4h后再灌注24h;复方甘草酸苷组动物缺血4h后给予复方甘草酸苷20mg/kg,再灌注24h;假手术组动物仅游离出股动脉不进行缺血,4h后缝合切口并给予等量生理盐水。主要观察指标:观察肌肉损伤后甘草酸苷对血浆乳酸脱氢酶、肌酸激酶活性及丙二醛浓度,肌组织髓过氧化物酶活性、湿质量/干质量比值及P-选择素mRNA表达水平的影响;光镜下观察骨骼肌的组织形态学改变。结果:假手术组的血浆肌酸激酶、乳酸脱氢酶活性和丙二醛浓度显著低于缺血再灌注组及复方甘草酸苷组(P<0.05),复方甘草酸苷组显著低于缺血再灌注组(P<0.01)。假手术组的骨骼肌组织髓过氧化物酶活性和湿质量/干质量比值显著低于缺血再灌注组及复方甘草酸苷组(P<0.01),复方甘草酸苷组显著低于缺血再灌注组(P<0.01)。10倍镜下坏死肌纤维数缺血再灌注损伤组显著大于复方甘草酸苷组(P<0.05)。骨骼肌组织中P-选择素mRNA表达水平假手术组显著低于缺血再灌注组(P<0.01),复方甘草酸苷组显著低于缺血再灌注组(P<0.05)。结论:复方甘草酸苷对骨骼肌缺血再灌注损伤有明显的保护作用。

BACKGROUND： The protective mechanism of glycyrrhizin concerning ischemia/reperfusion （I/R） is focus on cardiac muscle, kidney and intestine. Studies regarding skeletal muscle I/R are few. OBJECTIVE： To observe the effect of glycyrrhizin on ischemia/reperfusion injury in skeletal muscle of rabbits. DESIGN, TIME AND SETTING： The randomized controlled animal experiment was performed at the Key Laboratory of Medical Diagnostics, Ministry of Education, Chongqing Medical University from February 2008 to September 2008. MATERIALS： Twenty-four New Zealand rabbits, weighing 2.5-2.8 kg, were randomly divided into sham operation, model and glycyrrhizin groups, with 8 animals in each group. METHODS： Rabbits in the model group were established IR injury in right hind limb with ischemia 4 hours followed by 24 hours reperfusion. In the glycyrrhizin group, after 4 hours ischemia, rabbits were administrated 20 mg/kg glycyhrrizin, followed by 24 hours reperfusion. Rabbits in the sham operation group were infused with equal amount of physical saline. MAIN OUTCOME MEASURES： The effect of glycyrrhizin on plasma level of creatine kinase （CK）, lactic dehydrogenase （LDH）, malonaldehyde （MDA）, and the change of myeloperoxidase （MPO）, ratio of wet weight/dry weight （W/D） was observe; the expression of mRNA of p-selectin in the skeletal muscle after IR injury was checked. Histomorphological characteristics of the skeletal muscle were observed by light microscope. RESULTS： The plasma contents of CK, LDH, MDA in the sham operation group were obvious decreased than that of model and and glycyrrhizin groups （P 〈 0.05）, of which in the glycyrrhizin group was lower than the model group （P 〈 0.01 ）. The activity of MPO, W/D of skeletal muscle in the sham operation group was notably lower than that of glycyrrhizin and model groups （P 〈 0.01）, and glycyrrhizin group were significantly lower than that in model group （P 〈 0.01）. Compared with glycyrrhizin group, the number of necrotic muscle fibers was smaller in the model group under microscope （P 〈 0.05）. The expression of P-selectin mRNA in the sham operation group were significantly lower than that of the model group （P 〈 0.01）, glycyrrhizin group was lower than model group （P 〈 0.05）. CONCLUSION： Glycyrrhizin protects skeletal muscle against I/R injury in rabbits.