Effects of Carvedilol on Cardiomyocyte Apoptosis and Gene Expression In Vivo after Ischemia-Reperfus

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Summary: The effects of carvedilol on cardiomyocyte apoptosis and expression of bcl-2, bax genesfollowing ischemia (0. 5 h) and reperfusion (48 h) in vivo and the possible biological mechanism ofcarvedilol inhibiting cardiomyocyte apoptosis were studied. The left anterior descending artery inWistar rats were ligated to establish ischemia-reperfusion (I/R) models. The model animals were di-vided into two groups: I/R group, the model rats not subject to other treatments except ischemia-reperfusion (n=8); carvedilol-treated group (n= 8), I/R model rats treated with carvedilol. Eightrats in the sham-operated group were subjected to only experimental open operation. The number ofapoptotic cardiomyocyte was determined by TUNEL staining. Immunohistochemistry and in situ hy-bridization histochemistry (ISHH) were used to detect the expression of bcl-2 and bax genes. Imageprocessing system was used to quantitatively dispose the positive metric substances of both immuno-histochemistry and ISHH through the average optical density (OD) value. The results showed thatthe number of the apoptotic cells were 36. 18±9 (I/R group), 0-1 (sham-operated group) and 9.5±3 (carvedilol-treated group) in each visual field respectively with the difference being very significantamong the groups (P<0. 001). The OD values of bcl-2 protein in sham-operated group, I/R groupand carvedilol-treated group were 0. 14±0. 01, 0. 08±0. 02 and 0. 15±0. 03, respectively. The ODvalues of bcl-2 mRNA in sham-operated group, I/R group and carvedilol-treated group were 0. 08±0. 01, 0. 06 ±0. 01 and 0. 09 ±0. 01, respectively. There was no significant difference betweencarvedilol-treated group and I/R group (P> 0.05). The OD values of bax protein in I/R group,sham-operated and carvedilol-treated-treated group were 0. 13± 0. 02, 0. 07±0. 01, 0. 06± 0. 01, re-spectively. There was very significant difference between carvedilol-treated group and I/R group (P<0.01). Bcl-2/hax ratio was 1. 07±0.14 (I/R group), 1. 28±0.16 (sham-operated group), 2.5± 0. 26 (carvedilol-treated group) respectively with the difference being very significant betweencarvedilol-treated group and I/R group (P<0. 05). It was indicated that carvedilol could inhibit car-diomyocyte apoptosis following ischemia and reperfusion, which was related to the increased bcl-2/bax ratio due to inhibition of bax gene expression.
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