[SR 59230A on the expression of MicroRNAs in myocardium of heart failure rats].

Objective: To investigate the effects of β3-adrenoceptors(β3-AR) inhibitor SR 59230A on MicroRNAs expression in rat myocardium with chronic heart failure and the related mechanisms.

Methods: One hundred male SD rats were randomly divided into sham operated group(40)and chronic heart failure(CHF)group(60). Coronary artery ligation was used to induce CHF. Then the rats in CHF group were further randomly divided into CHF control group and CHF+SR 59230A group (CHF+SR). Rats in the sham group were divided into sham control group and sham+SR 59230A group (Sham+SR). The rats in Sham+SR group and CHF+SR group were treated with 1 ml SR 59230A(85 mmoL/L in 0.9% saline)twice a day for seven weeks by intraperitoneal injection, while the rats in control groups were injected with the same amount of saline for seven weeks separately. miScript miRNA PCR Arrays were used to determine the expression profile of MicroRNAs. Immunohistochemistry was used to evaluate the distribution of the related proteins in the heart tissue sections. Western blot was used to detect the expressions of nuclear factor-kappaB(NF-κB),p53 and p53-Phospho-Serine 15 in the heart.

Results: ①After blockade of β3-AR by SR 59230A, there were 18MicroRNAs down-regulated in sham control group and CHF control group. Within them, 6 MicroRNAs were related to NF-κB signaling pathway, they were miR-125b-5p,miR-143-3p,miR-145-5p,miR-26a-5p,miR-30a-5p and miR-320-5p. ②Slides from the heart tissue showed that NF-κB was distributed both in nucleus and cytoplasm, while p53 in cytoplasm was more than that in nucleus in heart tissue sections. The expressions of NF-κB and p53 were higher in the CHF control group than those in the sham control group(<0.05), but were lower in CHF+SR group than those in CHF control group(<0.05),while they were elevated in Sham+SR group compared to the sham control group(<0.05). ③ Compared with the sham control group, the protein expression of NF-κB p65 was increased significantly in the CHF control group (<0.05). After treated with SR59230A ,the protein expressions of NF-κB and p53-Phospho-Serine 15 were decreased significantly in CHF rats(<0.05),while the protein expressions of NF-κB, p53 and p53-Phospho-Serine 15 proteins were increased in the sham rats (<0.05).

Conclusions: Blocking of β3-AR improved the damaged heart in CHF rats; β3-AR caused the change of MicroRNAs expression, and it related to NF-κB signal pathway.