The effects of tanshinone IIA on hypoxia/reoxygenation-induced myocardial microvascular endothelial cell apoptosis in rats via the JAK2/STAT3 signaling pathway (Publication with Expression of Concern. See vol. 155, 2022) (Publication with Expression of Concern. See vol. 155, 2022)

Objective: This study aims to investigate the effects of tanshinone IIA on hypoxia/reoxygenation (H/R)-induced myocardial microvascular endothelial cell (MMEC) apoptosis in rats. Methods: MMECs from 10-days aged rats were isolated, cultured and identified, which were then divided into following groups: control group, control + tanshinone IIA (50 mu M) group, H/R model group, H/R + tanshinone IIA (5 mu M) group, H/R + tanshinone IIA (50 mu M) pre-treatment group, H/R + AG490 (50 mu M) pre-treatment group and H/R + AG490 (50 mu M) + tanshinone IIA (50 mu M) pre-treatment group. MTT assay, TUNEL staining and flow cytometry were used to measure the cellular viability and apoptosis. Western-blot were performed to detect protein expressions in JAK2/STAT3 signaling pathway. Results: Compared with control group, H/R group showed decreased cell viability, increased apoptosis rate, increased proportions of cells into G0/G1 phase, decreased proportions of cells in S phase and G2/M phase, as well as up-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, and down-regulated Bcl-2 expression (all P < 0.05). Compared with H/R group, H/R + tanshinone IIA (5 mu M) group, H/R + tanshinone IIA (50 mu M) group H/R + AG490 (50 mu M) group and H/R + AG490 (50 mu M) + tanshinone IIA (50 mu M) group had increased cell viability, decreased apoptosis rate, reduced proportions of cells into G0/G1 phase, elevated proportions of cells in S phase and G2/M phase, as well as down-regulated expressions of JAK2, STAT3, p53, Bax, Caspase-3, pJAK2 and pSTAT3, elevated expression of Bcl-2 (all P < 0.05). The most remarkable changes were observed in H/R + AG490 (50 mu M) + tanshinone IIA (50 mu M) group. Conclusion: Tanshinone IIA may attenuate H/R-induced MMEC apoptosis in rats by inhibiting the JAK2/STAT3 signaling pathway and regulating the expressions of p53, Bax, Caspase-3 and Bcl-2, which may provide a protective effect of tanshinone IIA for MMECs. (C) 2016 Elsevier Masson SAS. All rights reserved.