Protective effect of κ-opioid receptor agonist U50, 488 H pretreatment by intrathecal injection on myocardial ischemia/reperfusion injury / 中国生化药物杂志

ABSTRACT

Objective To explore the effect and mechanism of intrathecal injecting κ-opioid receptor agonist U50, 488H 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, 488H at 1 hour before they were underwent myocardial ischemia/reperfusion as in IR group.IV1 and IV2 groups were intravenous injected with U50, 488H respectively at the dose of 0.1 mg/kg and 0.01 mg/kg, while the IT group was intrathecal injected with U50, 488H at the dose of 0.01mg/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, 488H 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.