LIN Tingting,CHEN Chaoxing,BAO Nana, et al. Intervention of (Pyr1) Apelin-13 on PI3K/Akt pathway in bupivacaine-induced neonatal rat cardiomyocytearrest[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(2): 106-111.
Abstract：Objective: To explore the role and mechanism of Apelin/APJ system in myocardial toxicity of bupivacaine. Methods: Myocardial cells were extracted from neonatal mice for primary culture. The cells were
randomly divided into four groups: blank medium group (DMSO group), bupivacaine 1 mmol/L group (Bup
group), (Pyr1) Apelin-13 2 μmol/L group (Apl group) and bupivacaine 1 mmol/L+(Pyr1) Apelin-13 2 μmol/L group (BAp group). After the number of cell basal spontaneous beats were recorded in each group, the drug was administered according to the corresponding group for 6 h. The time after treatment was recorded as T0. The number of cell beats from T0 to T12 was recorded; the morphology of mitochondria in cardiomyocytes of T12 was observed by electron microscope; the content of LHD in cell culture medium by colorimetry; the concentration of Apelin-13 in cardiomyocytes of T12 was detected by ELISA. To detect the expression of APJ, PI3K, Akt, p-PI3K and p-Akt protein in cardiomyocytes of T12 was detected by Western blot. Results: All cardiomyocytes in Bup group stopped beating at T0. Compared with DMSO group, the number of cell beats was significantly decreased (P<0.05); mitochondria were swollen and vacuolated; the content of LDH in culture medium was significantly increased (P<0.05) and the expressions of Apelin-13, APJ, p-PI3K and p-Akt in cardiomyocytes were down-regulated (P<0.05) in Bup group. Compared with Bup group, the number of cell beats was significantly increased (P<0.05); the mitochondrial structure was obviously improved; the content of LDH in culture medium was significantly decreased (P<0.05) and the expression of Apelin-13, APJ, p-PI3K and p-Akt in cardiomyocyteswas up-regulated (P<0.05) in BAp group. Conclusion: (Pyr1) Apelin-13 can reverse bupivacaine-induced cardiomyocyte arrest, which may be related to the activation of PI3K/Akt protein phosphorylation
