鞘内注射阿片κ-受体激动剂U50,488H预处理对心肌缺血/再灌注损伤的保护作用  

Protective effect of κ-opioid receptor agonist U50,488H pretreatment by intrathecal injection on myocardial ischemia/reperfusion injury

作　　者：林家燕[1] 傅龙云 陈明生[1] 王亚斌[3] 曹丰[3] 

机构地区：[1]解放军第113医院麻醉科,浙江宁波315040 [2]舟山警备区医院外科,浙江舟山316000 [3]解放军第301医院心内科,北京271001

出　　处：《中国生化药物杂志》2016年第11期37-40,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：宁波市自然科学基金(2012A610239)

摘　　要：目的探讨鞘内注射阿片κ-受体激动剂U50,488H预处理对在体大鼠心肌缺血再灌注损伤的影响及相关机制。方法选择健康成年雄性SD大鼠随机分为5组:假手术组(Sham),模型组(IR),静脉注射高剂量组(IV1),静脉注射低剂量组(IV2),鞘内注射组(IT),采用大鼠在体心肌缺血/再灌注模型,Sham组完成所有手术操作,但左冠状动脉结扎线不打结,不予静脉或鞘内药物注射;IR组完成模型后,予心脏缺血30 min后再灌注120 min处理,不予静脉或鞘内药物注射;IV1组、IV2组及IT组在建立模型前1 h分别给予U50,488H预处理,IV1及IV2组分别静脉注射U50,488H 0.1 mg/kg及0.01 mg/kg,IT组鞘内注射U50,488H 0.01 mg/kg,而后予心脏缺血30 min后再灌注120 min处理,术后观察大鼠心脏超声、心肌天狼猩红染色,血浆降钙素基因相关肽(calcitonin generelated peptide,CGRP)及内皮素(endothelin,ET)含量等指标改变。结果心脏超声结果显示:与IR组(EF%=35.4±1.1,FS%=21.1±1.1)比较,IT组(EF%=49.1±1.2,FS%=27.1±1.0)及IV1组(EF%=46.3±2.2,FS%=26.6±0.6)均可明显改善缺血/再灌注损伤后大鼠心脏收缩功能(P<0.05),而IV2组(EF%=34.8±1.4,FS%=21.4±1.6)心功能无明显变化。心肌天狼猩红染色结果提示:与IR组比较,IT组及IV1组心肌纤维化损伤明显减轻,而IV2组则无明显改善。ELISA结果显示:与IR组比较,IT组及IV1组血清CGRP浓度明显增加(P<0.05),ET浓度明显减少(P<0.05),而IV2组均无明显统计学差异。结论鞘内注射阿片κ-受体激动剂U50,488H的预处理可明显改善大鼠心肌缺血/再灌注损伤后的心功能,并抑制心肌纤维化,其机制可能与调节CGRP、ET的释放有关。Objective To explore the effect and mechanism of intrathecal injecting κ- opioid receptor agonist U50,488 H on the rats with myocardial ischemia/reperfusion injury. Methods 50 Sprague – Dawley rats were randomly divided into five groups（ n = 10） ： sham group（ Sham）,ischemia/reperfusion group（ IR）,high-dose intravenous injection group（ IV1）,low-dose intravenous injection group（ IV2）,and intrathecal injection group（ IT）. In sham group the rats were followed by the modeling step without ligation of the left coronary and no drug injection by intravenous or intrathecal; in IR group the rats were underwent 30 minutes of myocardial ischemia followed by 120 minutes of reperfusion,and were not treated with any drug. All the rats in IV1,IV2 and IT groups were intravenous injected with U50,488 H at 1 hour before they were underwent myocardial ischemia/reperfusion as in IR group. IV1 and IV2 groups were intravenous injected with U50,488 H respectively at the dose of 0. 1 mg/kg and 0. 01 mg/kg,while the IT group was intrathecal injected with U50,488 H at the dose of 0. 01 mg/kg. All the rats from 5 groups were observed with cardiac ultrasound,myocardial sirius staining,serum CGRP and ET level. Results Compared to IR group（ EF% = 35. 4 ± 1. 1,FS% = 21. 1 ± 1. 1）,the rats in IT group（ EF% = 49. 1 ± 1. 2,FS% = 27. 1 ± 1. 0） and IV1 group（ EF% = 46. 3 ± 2. 2,FS% = 26. 6 ± 0. 6） showed better myocardial contraction（ P〈0. 05）and reduced myocardial fibrosis（ P〈0. 05）. IT group and IV1 group also showed reduced ET but increased CGRP in the serum（ P〈0. 05）. There were no difference between IV2 group and IR group in both observation. Conclusion Pretreatment with intrathecal injection of opium κ-receptor stimulant U50,488 H not only protected the myocardial function from myocardial ischemia/reperfusion injury,but also repressed myocardial fibrosis. The protection may result from modulation of CGRP and ET.

关 键 词：鞘内注射 阿片κ-受体 心肌缺血/再灌注 降钙素 

分 类 号：R542.2[医药卫生—心血管疾病] R543.3[医药卫生—内科学]