LongShengZhi capsule inhibits doxorubicin-induced heart failure by antioxidative stress
LongShengZhi capsule inhibits doxorubicin-induced heart failure by antioxidative stress
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龙生止胶囊抗氧化应激抑制阿霉素诱导的心力衰竭
DOI：
10.1016/j.biopha.2019.109803
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发表时间：
2020
影响因子：
7.5
通讯作者：
Yang Xiaoxiao
中科院分区：
文献类型：
--
作者：
Xu Shuai;Wang Yuanyu;Yu Maoyun;Wang D;an;Liang Yingquan;Chen Yuanli;Liao Chenzhong;Xie Zhouling;Zhao Buchang;Han Jihong;Duan Yajun;Yang Xiaoxiao
心力衰竭是世界范围内发病率和死亡率的主要原因。龙生芝胶囊是一种用于治疗血管疾病的中药制剂。在此，我们研究了LSZ治疗对多柔比星（DOX）诱导的小鼠心力衰竭的影响。C57 BL/6小鼠随机分为3组：对照组，正常饲料喂养; DOX组，腹腔注射DOX诱导心衰，正常饲料喂养; LSZ组，腹腔注射DOX，正常饲料喂养。DOX诱导心力衰竭，如血清肌酸激酶、乳酸脱氢酶和α-羟基丁酸脱氢酶升高和心脏纤维化所证明。然而，LSZ治疗实质上抑制了DOX诱导的心力衰竭参数。LSZ通过抑制I型胶原α1（COL 1 α1）、COL 1 α2、α-平滑肌肌动蛋白和转化生长因子β1的表达，降低胶原含量和纤维化。此外，阿霉素诱导的细胞凋亡抑制LSZ，再加上减少caspase 3的活性和mRNA的表达。LSZ降低炎性细胞因子水平。更重要的是，LSZ通过激活叉头框O3 A和沉默调节蛋白3诱导抗氧化应激酶的表达，包括超氧化物歧化酶1（SOD 1），SOD 2，过氧化氢酶和谷胱甘肽过氧化物酶1，从而降低氧化应激。总之，我们的研究表明，LSZ通过减少活性氧的产生和抑制炎症/细胞凋亡来减轻心力衰竭。我们的研究还表明LSZ在心力衰竭治疗中的潜在应用。
Heart failure is a major cause of morbidity and mortality worldwide. LongShengZhi capsule (LSZ), a traditional Chinese medicine, is used for treatment of patients with vascular diseases. Herein we investigated the effect of LSZ treatment on doxorubicin (DOX)-induced heart failure in mice. C57BL/6 mice randomly in 3 groups received following treatment: Control group, mice were fed normal chow; DOX group, mice were intraperitoneally injected DOX to induce heart failure and fed normal chow; and LSZ group, mice were injected DOX and fed normal chow containing LSZ. DOX induced heart failure as evidenced by increased serum creatine kinase, lactic dehydrogenase and α-hydroxybutyrate dehydrogenase, and cardiac fibrosis. However, LSZ treatment substantially inhibited DOX-induced heart failure parameters. Mechanistically, LSZ reduced collagen content and fibrosis by inhibiting expression of collagen type I α1 (COL1α1), COL1α2, α-smooth muscle actin and transforming growth factor β1. In addition, DOX-induced cell apoptosis was inhibited by LSZ, coupled with reduced caspase 3 activity and mRNA expression. LSZ decreased inflammatory cytokine levels. More importantly, LSZ decreased oxidative stress by inducing expression of anti-oxidative stress enzymes including superoxide dismutase 1 (SOD1), SOD2, catalase and glutathione peroxidase 1 through activation of forkhead box O3A and sirtuin 3. In conclusion, our study demonstrates that LSZ reduces heart failure by reducing production of reactive oxygen species and inhibiting inflammation/apoptosis. Our study also suggests the potential application of LSZ for heart failure treatment.