| Background:Acute myocardial infarction is a serious threat to human health. Reperfusion therapy has become the principal therapy to save the dying myocardium and to improve the prognosis.However, the ischemia-reperfusion injury (IRI) makes a big discount. Ischemia postconditioning(I-postC) could reduce myocardial injury. As the main constituent of GJ, redistribution and dysfunction of Connexin43(Cx43) has an important impact on the electrical couple of GJ, as well as RA and myocardial infarction size. MiRNA-1is one of important miRNAs involved in IRI. Its overexpression can aggravate IRI. Some studies have shown that Cx43is one of the targets of miRNA-1. However, during I-postC, it is still unclear whether miRNA-1could participate the regulation of IRI by affecting the expression and distribution of Cx43.Objective:l.To observe the effect of I-postC on the distribution and expression of Cx43and miRNA-1and effect on IRI.2. To observe the effect of miRNA-1on. distribution and expression of Cx43in isolated rat heart during I-postC.Method:55Wistar male rats were randomly divided into5groups:normal (N) group, ischemia-reperfusion(I-R)group, ischemia postconditioning(I-postC)group, agomir-1+I-postC (agomir-1)group and antagomir-1+I-postC (antagomir-1) group. Agomir-1group and antagomir-1group were respectively accepted agomir-1(100pmol.kg-1.d-1) and antagomir-l(200pmol.kg-1.d-1) with tail vein injection for3days. After anesthesia and anticoagulation, the hearts were excised and perfused with Langendorff system. N group:no ligation of LAD. I-R group:ligation for30min, followed by reperfusion. I-postC group, agomir-1group and antagomir-1group:ligation for30min, followed by I-postC, and RA, LVDP, and myocardial infarct size were recorded and observed. With RT-PCR, Western Blot and immunehistochemistry, to observe the expression of miRNA-1and the expression and distribution of Cx43. SPSS20.0software was applicated for statistical analysis, statistical significance was set at P<0.05.Results:1. About RA score:RA score for I-R group were higher (P<0.01) than N group; while there is no difference between I-postC and antagomir-1group. Agomir-1 group achieved a higher score than I-postC group (P<0.01).2.About the LVDP:The baseline of LVDP is of no difference in5groups. At ischemic state, LVDP of groups for ligation were reduced (P<0.01). Reperfusion state, LVDP in I-R and agomir-1group were continously decreased and lower than N group (P<0.01), and I-postC and antagomir-1group were back to the level of N group(P>0.05). LVDP in agomir-1group was lower than I-postC group (P<0.05).3. About myocardial infarct area: myocardial infarct area in I-R group, I-postC group, agomir-1group and antagomir-1group were (50.44±1.39)%,(27.58±1.05)%,(62.72±1.20)%and (27.25±1.29)%respectively. In I-R and agomir-1group it was larger than that in the I-postC and antagomir-1group. And there was no difference between antagomir-1group and I-postC group (P>0.05).4. Expression of miRNA-1in I-R group was2.6folds higher than that in N group. Compared with I-R group, the expression of I-postC group decreased50%(P<0.01). Moreover it was increased78%in agomir-1group but decreased32%in antagomir-1group comparing with I-postC group(P<0.01).5. Compared with N group, Cx43expression in I-R group was reduced. In I-postC group it was increased to N group level. In agomir-1group it decreased but was still more than I-R group, antagomir-1was same to I-postC group.6. In I-R and agomir-1group the distribution of Cx43was irregular and disorganized. While in I-postC and antagomir-1group, it increased at intercalated disc, and at side to side only a small amount of distribution can also be found.Conclusion:1. I-postC can reduce the incidence of RA and infarct area and improve LVDP. Meanwhile it can suppress the reduction and redistribution of Cx43and suppress the overexpression of miRNA-1induced by ischemia reperfusion.2. During I-postC, the downregulation of miRNA-1can prevent Cx43from decresing and redistribution to protect the heart from IRI. |
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