Excessive platelet apoptosis is one of the pathogenic causes of immune-induced bone marrow failure (BMF). The aim of the present study was to explore the role of mitochondria-mediated pathway in the apoptosis of platelets in immune-induced BMF. An immune-induced BMF model was established in mice, which were randomly divided into three groups: normal control (CTL) group, BMF group and cyclosporine (CSA) group (n = 10 in each group). Mice were given 0.027 g/kg CSA daily in the CSA group. Platelet count (PLT), mitochondrial transmembrane potential (Delta Psi m), cytochrome C (CytC), phosphatidylserine (PS), calcium ion (Ca2+) and expression of proteins of the mitochondrial apoptotic pathway, including Bak, Bax, caspase-3, caspase-8 and caspase-9, was examined and compared. Compared with the CTL group, the BMF group had significantly a lower level of PLC and Delta Psi m, but higher levels of CytC, PS, Ca2+ and higher expression levels of Bak, Bax, cleaved caspase-9 and cleaved caspase-3 (P < 0.05). CSA restored the above changes in the BMF model (P < 0.05). Further studies showed that intravenous injection of the caspase-9 inhibitor Z-LE(OMe) HD(OMe)-fluoromethylketone (FMK) into the mice could significantly inhibit apoptosis of the platelets and the effect of CSA treatment when compared to the BMF group, and exerted a better protective effect from apoptosis if the caspase-9 inhibitor was combined with the CSA treatment. These results revealed that platelet apoptosis may play an important role in the reduction of platelet of immune-induced BMF probably through the mitochondrial pathway.
[1]Shanghai Univ Tradit Chinese Med, Shanghai Baoshan Hosp Integrated Tradit Chinese &, Dept Hematol, Baoshan Branch,Shuguang Hosp, Shanghai 201999, Peoples R China.
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