| Object:To observe the cardioprotective effects and discuss the mechanism of dioscin on myocardial ischemia reperfusion injury in rats,such as physiology,infarct size, morphologic changes and biochemistry after myocardial IR.Methods:Male Wistar rats were randomly divided into 4 groups:IR group,dioscin high dose(D_H) group and dioscin low dose(D_L) group.The IR group was treated with NS 10mL/kg.d for 7 days,D_H group and D_L group were treated with dioscin 300mg/kg.d and 150 mg/kg.d respectively for 7 days.24 hours after the last oral injection,in IPC group,the LAD of rats were occluded three times each for 5 minutes, followed by reperfusion for 5 minutes(IPC);while rats in IR and D_H,D_L groups were subjected to no treatment for 30 minutes followed by reperfusion for 2 hours. Observe the effects on myocardial physiology(HR,MAP,ST-segment),the onset and duration of ventricular arrhythmia(VA),the score of arrhythmia.The activity of plasma creatine kinase(CK),nitrogen monoxidum(NO) was measured before ischemia,30 minutes after ischemia and 2 hours after reperfusion.At the end of reperfusion,HE and TTC stainings were performed to determine myocardial necrosis;or the activity of cardiac muscle's??eroxide dismutase(SOD),the quantity of malondialdehyde(MDA) were measured;or total RNA was extracted and levels of mRNA expression of Mn-SOD were measured by RT-PCR.ResultsI Study on the physiological effects of dioscin against myocardial ischemia reperfusion injury in ratsThe incidence of VA:IR group(81.25%),IPC group(0%),D_H group(0%) and D_L group(12.5%),compared with IR group(P＜0.01).No obvious difference was observed between D_H and D_L group.Onset and duration time of ventricular premature contraction:IR group (3.82±1.33;21.69±4.79),IPC group(12.97±2.82;10.21±2.84),D_H group (14.07±3.29;8.76±2.99) and DLgroup(10.34±2.73;11.64±3.69),group(P＜0.01). No obvious difference was observed between D_H and D_L group.Onset and duration time of ventricular tachycardia:IR group(6.81±1.84; 17.26±2.97),IPC group(16.74±2.97;9.43±2.14) D_H group(18.88±1.76; 7.54±1.79) and DL group(14.44±2.77;10.39±2.94),compared with IR group (P＜0.01).No obvious difference was observed between D_H and D_L group.The elevation of ST-segment during ischemic period IPC group(0.331±0.048 mV) D_H group(0.305±0.032mV) and DLgroup(0.370±0.027 mV),compared with IR group(P＜0.01).No obvious difference was observed between D_H and DL group.Ⅱ.Study on the infarct size and morphologic change of dioscin against myocardial ischemia reperfusion injury in ratsIR group,the myocardial infarct size was extensive(48.59±9.84%);IPC group, the myocardial infarct size was reduced obviously(24.03±5.12%);D_H group,the myocardial infarct size was reduced remarkably(21.48±2.72%);D_L group,the myocardial infarct size was reduced remarkably(23.86±5.65%);compared with IR group(P＜0.01).No obvious difference was observed between D_H and D_L group.ⅢStudy on the biochemistry and the expression of Mn-SOD of dioscin against myocardial ischemia reperfusion injury in ratsIR group:the plasma CK corresponding to reperfusion injury was increased remarkably(122.55±18.11 U/L).IPC group:the elevation of plasma CK corresponding to reperfusion injury was reduced significantly(98.15±12.5U/L);DH group:the elevation of plasma CK corresponding to reperfusion injury was reduced significantly (92.37±13.96U/L);D_L group:the elevation of plasma CK corresponding to reperfusion injury was reduced significantly(99???5.38 U/L) compared with IR group(P＜0.01). No obvious difference was observed between D_H and D_L group.IR group:the plasma NO corresponding to ischemic injury was reduced remarkably(23.53±5.81 U/L) and increased obviously during reperfusion(31.03±5.86 U/L).IPC group:the decrease of plasma NO corresponding to ischemic injury was reduced significantly(30.54±4.80U/L) and the elevation during reperfusion was increased obviously(40.95±7.98 U/L),compared with IR group(P＜0.05).D_H group: the decrease of plasma NO corresponding to ischemic injury was reduced significantly(35.48±6.88U/L) and the elevation during reperfusion was increased remarkably(44.70±11.07 U/L),compared with IR group(P＜0.01).No obvious difference was observed between D_H and D_L group.D_L group:the decrease of plasma NO corresponding to ischemic injury was reduced significantly(32.74±9.83U/L) and the elevation during reperfusion was increased obviously(41.59±9.34 U/L),compared with IR group(P＜0.05).No obvious difference was observed between D_H and D_L group.IR group:The quantity of MDA(2.87±0.89 nmol/mg);IPC group:the quatity of MDA was decreased(1.62±0.69 nmol/mg);D_H group:the quatity of MDA was decreased remarkably(1.44±0.30 nmol/mg);D_L group:the quatity of MDA was decreased obviously,compared with IR group(P＜0.01).No obvious difference was observed between D_H and D_L group.IR group:the activity of SOD(T-SOD 158.73±16.21 U/prog;Mn-SOD 60.69±19.29 U/prog),IPC group:the activity of SOD was increased obviously(Mn-SOD 105.19±30.62U/prog),D_H group:the activity of SOD was increased remarkably (T-SOD 215.74±18.31U/prog;Mn-SOD 116.46±19.56U/prog),D_L group:the activity of SOD was increased remarkably(T-SOD 198.19±29.09U/prog;Mn-SOD 108.61±28.88 U/prog),compared with IR group(P＜0.01).No obvious difference was observed between D_H and D_L group.IR group(0.45±0.12),IPCgroup(0.68±0.09),D_H group(0.76±0.11) and D_L group(0.71±0.12),compared with IR group(P＜0.01).No obvious difference was observed between D_H and D_L group.Conclusion:The results document that dioscin protects myocardium from IR injury by decreasing the extent of ischemia-induced VA,the infarct size,and the activity of plasma CK during reperfusion,as well as the quantity of MDA in cardiac muscle while increasing plasma NO,the expression of Mn-SOD in m-RNA,the activity of Mn-SOD in cardiac muscle.The mechanism of cardioprotective effects of dioscin is related with abating the oxygen free radical injury and protecting blood vessel endothelium.
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