内啡肽-1后处理对大鼠心肌缺血再灌注损伤的实验研究

目的:观察内啡肽-1(EM-1)后处理对大鼠心肌缺血再灌注损伤的影响。方法:健康雄性SD大鼠48只,随机分为8组:假手术组(S组),缺血再灌组(IR组),缺血后处理组(IPO组),EM-1后处理10、20和50μg/kg(EM10、EM20、EM50)三组,EM-1 50μg/kg+纳洛酮3mg/kg后处理组(EM50+Nal组)、Nal后处理组(Nal组),均i.v.给药。结扎冠脉左前降支30min,再灌120min造IR模型。全程监测心率(HR)、平均动脉压(MAP)和Ⅱ导联心电图(ECG)。动脉血浆检测丙二醛(MDA)含量及乳酸脱氢酶(LDH)和超氧化物歧化酶(SOD)的活性。结果:除EM各组再灌注120min MAP外,IPO组和EM各组HR、MAP、RPP的下降程度均显著低于IR组(P<0.05,P<0.01);与IR组比较,IPO组和EM-1三个剂量组均使血浆LDH活性降低、MDA含量降低及SOD活性增加(P<0.05,P<0.01),且EM对MDA含量及SOD活性的影响呈剂量依赖;与EM50组比较,EM50+Nal组血浆LDH活性升高、MDA含量增加及SOD活性降低(P<0.05,P<0.01)。结论:EM-1后处理可能是通过激动阿片受体,引起MDA含量降低及SOD活性增加,发挥对心肌缺血再灌注损伤的保护作用。

The Stability of Endomorphin-1 Solution

Aim To study the most stable pH value of endomorphin-1 solution and toestimate the shelf-life of EM-1 solution. Methods The content of EM-1 in its solution was determinedby HPLC, and stability was studied by accelerated tests. Results The most stable pH value of EM-1solution was observed. By the accelerated tests we obtained the Arrhe-nius relationship and thepharmacokinetic parameters. Conclusion The most stable pH value of EM-1 solution is 4.5 -4.8. Thet_(1/2)(25℃) is 45 d.

μ阿片受体外显子7在大鼠EM-1镇痛中的作用

目的:研究μ阿片受体外显子-7在EM-1镇痛中的作用。方法:取大鼠鞘内置管成功造模,随机分为3组,对照组,N-siRNA组及E-siRNA组,每组8只,每组分别经鞘内给予生理盐水30μl,阴性siRNA20μl质粒(NsiRNA组),或阳性siRNA 20μl质粒(E-siRNA组),连续处理3d,每天一次,于第4天检测机械痛觉,在基础机械痛阈检测后1h注射药物,大鼠分别于鞘内注射10μg的EM-1,于药物注射后5min,20min,40min及60min时间点检测机械性缩足反射痛阈值。E-siRNA组在上述实验结束6h后给予EM-1,10μg加10μg的纳洛酮,重复5min,20min,40min时间点检测痛阈值。结果:各组间的基础机械痛阈无差别;E-siRNA组EM-1的镇痛效能未降低(P>0.05),但表现延迟现象,在20min时达到最大;E-siRNA组在EM-1加纳洛酮未显示镇痛作用。结论:鞘内注射的靶向μ阿片受体外显子-7的阳性siRNA,对基础机械痛阈无影响;对EM-1的镇痛作用有延迟作用但未降低其镇痛效能。