Abstract: Objective · To observe mitochondria permeability transition pore (mPTP) opening and apoptosis of H9c2 myocardial cell stimulated by lipopolysaccharide (LPS), and to explore the anti-apoptotic effect of combined application of cyclosporine A (CsA) and ryanodine (Rya).  Methods · The H9c2 cells were divided into Control group, LPS group, LPS+CsA group, LPS+Rya group, and LPS+CsA+Rya group. The mPTP opening state, Ca2 + concentration within cell and mitochondrial, mitochondrial membrane potential (ΔΦm), cell apoptosis, expression of Bax and Bcl-2 at mRNA and protein levels, and activity of caspase 3 were determined respectively.  Results · mPTP opened after being stimulated by LPS for 24 h, which increased the fluorescence intensity for Ca2+ in cytosolic and mitochondria by 298% and 231% respectively, induced about 1/3 cell apoptosis, improved the activity of caspase 3 approximately twice, and enhanced expression of Bax mRNA (P=0.008). The combined use of CsA and Rya effectively inhibited mPTP opening, increased the enhancement of fluorescence intensity for Ca2+ in both cytosolic and mitochondria, maintained normal ΔΦm, reduced LPS-induced apoptosis, inhibited the activity of caspase 3, and decreased Bax mRNA expression level induced by LPS in the myocardial cells.  Conclusion · mPTP plays an important role in in LPS-induced myocardial apoptosis, whereas the combination of CsA and Rya can alleviate it effectively.

Key words: cardiac myocyte, mitochondria permeability transition pore, lipopolysaccharide, cyclosporine A