钙离子阻滞剂异搏定对挤压伤大鼠保护作用的实验研究

Protective effect of calcium channel blocker in rats with crush injury

目的研究钙离子阻滞剂(calcium channel blocker,CCB)盐酸维拉帕米(异搏定)对挤压伤大鼠的保护作用和可能机制。方法首先建立挤压伤模型,将40只SD大鼠随机分为4组(每组10只);分别为:对照组(A)、一般治疗组(B)、早期钙离子阻滞剂异搏定治疗组(C)、解压后钙离子阻滞剂异搏定治疗组(D)。分别检测在解压前5min和解压后3h各组大鼠血清肌酸激酶(creatine kinase,CK)、丙二醛(maleic dialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)水平。并统计72h后各组大鼠的存活率。结果对照组血清MDA、CK水平明显低于其他各挤压伤组(P<0.01),血清SOD水平在解压前低于各挤压伤组(P<0.01)。应用钙离子阻滞剂治疗组血清MDA、CK水平明显低于一般治疗组(P<0.01)。在解压前,早期钙离子阻滞剂治疗组血清SOD含量明显高于其他挤压伤组(P<0.01)。而解压后钙离子阻滞剂治疗组血清SOD水平明显高于一般治疗组(P<0.01)。存活率比较亦提示钙离子阻滞剂治疗组优于一般治疗组。结论钙离子阻滞剂对挤压伤所致损伤具有保护作用。挤压伤所引起损伤的发病机制可能与肌细胞钙离子浓度改变有关。其机制可能为阻断机械和缺血再灌注导致的肌细胞内钙离子浓度改变对细胞的损伤。

Objective To observe the protective effect of calcium channel blocker（Verapamil hydrochloride） on crush injury and its possible mechanisms.Methods Rat crush injury model was prepared as follows： 40 SD rats were assigned into 4 groups randomly,including control group,routine resuscitation group,and treatment group in which Verapamil hydrochloride was administered either at the early stage or after the crush injury.Blood samples were collected at 5 minutes before decompression and 3 hours after decompression.Serum MDA,CK and activities of SOD were examined.The survival rate of each groups was monitored 72 hours after the crush injury.Results Serum CK and MDA in crush injury groups were significantly higher than those in control group（P0.01.Serum SOD activity of the crush groups before decompression was significantly higher than that in control group（P0.01）.Serum levels of CK and MDA in Verapamil hydrochloride resuscitation groups were lower than those in the routine resuscitation group（P0.01.Before decompression,serum SOD activity in early Verapamil hydrochloride resuscitation groups was significantly lower than that of other crush groups（P0.01）.After decompression,serum SOD activity in Verapamil hydrochloride resuscitation groups was significantly higher than that in routine resuscitation group（P0.01）.The mortality of Verapamil hydrochloride resuscitation groups was also improved as compared to the routine resuscitation group.Conclusion Calcium channel blocker（Verapamil hydrochloride）resuscitation may be an effective therapeutic method for crush injury,at least partly,through inhibiting deleterious change of Ca2＋ concentration in muscle cell resulting from mechanical stress and ischemia-reperfusion injury.