| Objective: To investigate the effect of nicorandil(Nic) on brain natriureticpeptide(BNP), matrix metalloproteinases-9(MMP-9), tissue inhibitors ofmetalloproteinases-1(TIMP-1) and connexin43（Cx43） expression in myocardium ofa rat model of myocardial hypertrophy induced by isoprenaline(ISO), and investigatethe possible mechanisms.Methods: Myocardial hypertrophy model was established using subcutaneousinjection of ISO.50SD rats were randomized into the control group(group A),myocardial hypertrophy model group(group B), Nic group(group C), theco-administration of nicorandil and glibenclamide(Glib) group(group D), and Glibgroup(group E). Group C rats were treated with Nic (5mg/kg·d)stomachically.Group D rats were treated with Nic (5mg/kg·d) and Glib(5mg/kg·d) stomachically.IN glibenclamide treatment,5mg/kg·d was fed stomachically in the group E.Equivalent distilled water was used in the group A and B. Heart mass index(HMI) andleft ventricular mass index(LVMI) were calculated. The serum level of BNP wasmeasured by enzyme-linked immunosorbent assay(ELISA). The expression ofMMP-9, TIMP-1and Cx43in heart tissue was analyzed by Immunohistochemistry.Results:(1) Comparing with the control group, HMI, LVMI, BNP and the expression ofMMP-9were significantly increased(P<0.05) in the group B, group C, group Dand group E, the expression of TIMP-1was significantly decreased (P<0.05).Cx43distribution was changed and the expression was significantly decreased(P<0.05). (2) After treatment with Nic in the myocardial hypertrophy group, HMI, LVMI, BNPand the expression of MMP-9in the group C were significantly decreased(P<0.05)comparing with group B, the expression of TIMP-1was significantlyincreased(P<0.05), the derangement of Cx43distribution was reversed and itsexpression was increased(P<0.05).(3) When combined use of Glib, the potassium channel blocker, the BNP level, theexpression of MMP-9in the group D and E were significantly increased(P<0.05)compared to that in the group C, while the expression of TIMP-1andCx43were significantly decreased (P<0.05), but that difference was notstatistically significant (P>0.05) compared with group B.Conclusion:(1) ISO induced myocardial hypertrophy in SD rats, with the BNP level and thepositive rate of MMP-9expression increased, the positive rate ofTIMP-1expression decreased, Cx43distribution changed and the positive rate ofCx43decreased.(2) Treatment with Nic, the BNP level and the positive rate of MMP-9decreased inmyocardial hypertrophy rats, the positive rate of TIMP-1and Cx43increased.(3) Glib can remarkably attenuate the anti-hypertrophy effects of nicorandil, whichindicate that nicorandil can improve cardiac hypertrophy by opening KATPchannel. |
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