Influence of proteasome inhibitor MG-132 on the expression of Hsp 70 and myocardial apoptosis after myocardial infarction

Objective: This study aims to explore the influence of proteasome inhibitor MG-132 on the expression of Hsp70 and myocardial apoptosis after myocardial infarction. Methods: A myocardial infarction (MI) model was established. The animals used for this study were randomized into four groups: MI group (n=6), MG group (n=6), MG+quercetin (MG+Q) group (n=6), and sham-operation group (SH) (n=6). On the next day after surgery, the MG group was administered with MG-132 via intraperitoneal injection, the MG+Q group received MG-132 and quercetin via intraperitoneal injection, and MI and SH groups were administered with normal saline (NS) after the surgery for 28 days. Animals were sacrificed by inhalation of carbonic oxide, and the samples were collected. RT-PCR assay was used to detect the mRNA expression of heat shock protein 70 (Hsp70), and immunohistochemistry and western blot assays were performed to detect the protein expression of Hsp70 and caspase-3. TUNEL method was used to detect the myocardial apoptosis of tissues around the infarction area. Results: The apoptosis index of cells surrounding the non-infarction area in the SH, MI, MG and MG+Q groups was 0.89 ± 0.12, 21.31 ± 0.82, 5.27 ± 0.51 and 7.15 ± 0.41, respectively. Compared with the SH group, the apoptosis indexes in the MI, MG and MG+Q groups significantly increased (P<0.01). Compared with the MI group, the apoptosis indexes of myocardial cells in the MG and MG+Q groups significantly decreased (P<0.01), especially in the MG group (P<0.01). The difference in the mRNA and protein expression of Hsp70 between the SH and MI groups was not statistically significant (P>0.05). Compared with the SH and MI groups, the mRNA and protein expression of Hsp70 in the MG and MG+Q groups significantly increased (P<0.01), especially in the MG group (P<0.01). Compared with the SH group, the protein expression of caspase-3 in the MI, MG and MG+Q groups significantly increased (P<0.01). Compared with the MI group, the expression of caspase-3 in the MG and MG+Q groups significantly decreased (P<0.01), especially in the MG group (P<0.01). Conclusions: (1) A small dosage of proteasome inhibitor MG-132 reduced the apoptosis of myocardial cells in the non-infarction area after myocardial infarction. (2) MG-132 may inhibit the apoptosis of myocardial cells by increasing the expression of Hsp70 and inhibiting the expression of caspase-3.

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