ABSTRACT
Objective To evaluate the relationship between macrophage migration inhibitory factor ( MIF) expression and obese-induced abolition of sevoflurane preconditioning-induced cardioprotection in mice. Methods Forty-eight male C57BL∕6J mice, aged 4 weeks, were divided into 2 groups ( n=24 each) using a random number table method: normal diet group ( Lean group ) and high-fat diet group ( Obese group) . Lean group were fed a normal diet ( 10％ kcal) for 12 weeks, while Obese group were fed a high-fat diet ( 60％ kcal) for 12 weeks. The weight of mice was measured. Blood samples were collected from the tail vein for determination of blood glucose concentrations, and plasma concentrations of total cho-lesterol, triglyceride, insulin and leptin. After measurement of the parameters mentioned above, Lean group and Obese group were divided into 3 subgroups ( n=8 each) using a random number table method:sham operation groups (L-Sham group, O-Sham group), myocardial ischemia-reperfusion groups (L-IR group, O-IR group) and sevoflurane preconditioning groups (L-IR+Sev group, O-IR+Sev group). The mice were anesthetized and their hearts were immediately removed and retrogradely perfused in a Langendorff apparatus with an oxygenated K-H solution at 37 ℃. Hearts were continuously perfused with K-H solution for 115 min in L-Sham and O-Sham groups. Hearts were subjected to global ischemia for 25 min, followed by 60-min reperfusion after being retrogradely perfused with K-H solution in L-IR and O-IR groups. In L-IR+Sev and O-IR+Sev groups, hearts were subjected to 3 cycles of 5-min perfusion with sevoflurane-contai-ning K-H solution ( final concentration 0. 6 mmol∕L) and 5-min washout, and then hearts were subjected to global ischemia for 25 min, followed by 60-min reperfusion. Left ventricular developed pressure ( LVDP ) , left ventricular end-diastolic pressure ( LVEDP ) , and the maximum rate of increase or decrease in left ventricular pressure ( ±dp∕dtmax) were recorded at the end of reperfusion. Hearts were obtained at the end of reperfusion for determination of myocardial infarct size and expression of MIF ( by Western blot) . Results Compared with Lean group, the weight, blood glucose, levels of plasma total cholesterol, tri-glyceride, insulin and leptin were significantly increased in Obese group (P<0. 05). Compared with L-Sham group, the LVDP and +dp∕dtmax were significantly decreased, LVEDP and -dp∕dtmax were in-creased, myocardial infarct size was increased, and the expression of myocardial MIF was up-regulated in L-IR and L-IR+Sev groups, and the expression of myocardial MIF was up-regulated in O-Sham group ( P<0. 05) . Compared with L-IR group, LVDP and +dp∕dtmax were significantly increased, LVEDP and-dp∕dtmax were decreased, myocardial infarct size was decreased, and the expression of myocardial MIF was up-regulated in group L-IR+Sev, and the expression of myocardial MIF was significantly up-regulated in group O-IR (P<0. 05). Compared with O-Sham group, LVDP and +dp∕dtmax were significantly de-creased, LVEDP and-dp∕dtmax were increased, and myocardial infarct size was increased, and no signif-icant change was found in the expression of MIF in O-IR and O-IR+Sev groups ( P>0. 05) . Conclusion The mechanism by which obese abolishes sevoflurane preconditioning-induced cardioprotection may be relat-ed to inducing MIF over-expression in mice.