METHODS: The cardioprotective effects and mechanisms of L-theanine and the role of Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling were investigated in MIRI mice using measures of cardiac function, oxidative stress, and apoptosis.
RESULTS: Administration of L-theanine (10 mg/kg, once daily) suppressed the MIRI-induced increase in infarct size and serum creatine kinase and lactate dehydrogenase levels, as well as MIRI-induced cardiac apoptosis, as evidenced by an increase in Bcl-2 expression and a decrease in Bax/caspase-3 expression. Administration of L-theanine also decreased the levels of parameters reflecting oxidative stress, such as dihydroethidium, malondialdehyde, and nitric oxide, and increased the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in ischemic heart tissue. Further analysis showed that L-theanine administration suppressed the MIRI-induced decrease of phospho-JAK2 and phospho-STAT3 in ischemic heart tissue. Inhibition of JAK2 by AG490 (5 mg/kg, once daily) abolished the cardioprotective effect of L-theanine, suggesting that the JAK2/STAT3 signaling pathway may play an essential role in mediating the anti-I/R effect of L-theanine.
CONCLUSIONS: L-theanine administration suppresses cellular apoptosis and oxidative stress in part via the JAK2/STAT3 signaling pathway, thereby attenuating MIRI-induced cardiac injury. L-theanine could be developed as a potential drug to alleviate cardiac damage in MIRI.
方法:研究了L-茶氨酸的心脏保护作用和机制以及Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)信号传导在MIRI小鼠中的作用心脏功能,氧化应激,和凋亡。
结果:施用L-茶氨酸(10mg/kg,每天一次)抑制了MIRI诱导的梗死面积和血清肌酸激酶和乳酸脱氢酶水平的增加,以及MIRI诱导的心肌细胞凋亡,如Bcl-2表达增加和Bax/caspase-3表达减少所证明。施用L-茶氨酸也降低了反映氧化应激的参数水平,如二氢乙锭,丙二醛,和一氧化氮,并增加了反映抗氧化的参数水平,如总抗氧化能力(T-AOC),谷胱甘肽(GSH),和缺血心脏组织中的超氧化物歧化酶(SOD)。进一步分析显示L-茶氨酸给药抑制了MIRI诱导的缺血心脏组织中磷酸-JAK2和磷酸-STAT3的减少。AG490对JAK2的抑制作用(5mg/kg,每天一次)消除了L-茶氨酸的心脏保护作用,提示JAK2/STAT3信号通路可能在介导L-茶氨酸抗I/R效应中起重要作用。
结论:L-茶氨酸通过JAK2/STAT3信号通路抑制细胞凋亡和氧化应激,从而减轻MIRI诱导的心脏损伤。L-茶氨酸可作为减轻MIRI心脏损伤的潜在药物。