Li Zhengtao, Li Sujuan, Hu Lin, Li Fang, Cheung Alex Chun, Shao Weizai, Que Yuling, Leung George Pek-Heng, Yang Cui
Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, P.R. China.
Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
Afr J Tradit Complement Altern Med. 2017 Jan 13;14(2):241-252. doi: 10.21010/ajtcam.v14i2.26. eCollection 2017.
As a bioactive composite extracted from American cockroach, injection (XML) is used for the treatment of congestive heart failure (CHF) in China. Clinical data has provided evidence that XML has positive inotropic properties. The objective of this study was to assess the mechanisms involved in the therapeutical effect of XML on CHF.
The effects of XML on the cardiac function in isolated rat heart were measured. A Ca imaging technology was used in rat cardiomyocytes (H9c2 cells) to reveal the role of XML on Ca channels. Meanwhile, the effects of XML on the activities of Na+/K+ ATPase and sodium/calcium exchanger were measured. In addition, the level of reactive oxygen species and the protein expressions for the superoxide dismutase and hemeoxygenase were determined in the cardiomyocytes.
The results showed that XML increased the electrical impulse-induced [Ca] in H9c2 cells, which was dependant on extracellular Ca and was abolished by ML218-HCl (a T-type Cachannels antagonist) but not nimodipine (a L-type Cachannels antagonist). Ouabain, a Na+/K+-ATPase inhibitor, increased the electrical impulse-induced [Ca], which was significantly inhibited by XML. Moreover, XML markedly inhibited the Na+/K+ ATPase activity in H9c2 cells. In addition, XML notably reduced the production of reactive oxygen species and enhanced the protein expressions of antioxidant enzymes including superoxide dismutase 1, superoxide dismutase 2 and hemeoxygenase 1 in H9c2 cell.
Our findings pave the ways to the better understandings of the therapeutic effects of XML on cardiovascular system.
作为从美洲大蠊中提取的一种生物活性复合物,心脉隆注射液(XML)在中国用于治疗充血性心力衰竭(CHF)。临床数据已证明XML具有正性肌力作用。本研究的目的是评估XML治疗CHF的作用机制。
测定XML对离体大鼠心脏心功能的影响。利用钙成像技术在大鼠心肌细胞(H9c2细胞)中揭示XML对钙通道的作用。同时,测定XML对Na+/K+ATP酶和钠/钙交换体活性的影响。此外,还测定了心肌细胞中的活性氧水平以及超氧化物歧化酶和血红素加氧酶的蛋白表达。
结果显示,XML增加了H9c2细胞中电冲动诱导的[Ca],这依赖于细胞外钙,且被ML218-HCl(一种T型钙通道拮抗剂)所消除,但不被尼莫地平(一种L型钙通道拮抗剂)所消除。哇巴因,一种Na+/K+-ATP酶抑制剂,增加了电冲动诱导的[Ca],而XML可显著抑制这种增加。此外,XML显著抑制H9c2细胞中的Na+/K+ATP酶活性。另外,XML显著降低了H9c2细胞中活性氧的产生,并增强了抗氧化酶包括超氧化物歧化酶1、超氧化物歧化酶2和血红素加氧酶1的蛋白表达。
我们的研究结果为更好地理解XML对心血管系统的治疗作用铺平了道路。