The oxygen radical generator pyrogallol impairs cardiomyocyte contractile function via a superoxide and p38 MAP kinase-dependent pathway: protection by anisodamine and tetramethylpyrazine.
The oxygen radical generator pyrogallol impairs cardiomyocyte contractile function via a superoxide and p38 MAP kinase-dependent pathway: protection by anisodamine and tetramethylpyrazine.
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DOI：
10.1385/ct:4:4:375
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发表时间：
2004-01-01
影响因子：
3.2
通讯作者：
Ren, Jun
中科院分区：
文献类型：
--
作者：
Esberg, Lucy B;Ren, Jun
氧源性自由基已被证明有助于心肌功能障碍的发病机制，尽管其潜在机制仍未完全了解。本研究旨在探讨超氧化物生成物邻苯三酚对心脏收缩功能的作用，以及中药山莨菪碱和川芎嗪（TMP）对邻苯三酚诱导的心脏收缩反应的可能干预。分离成年大鼠心室肌细胞并刺激其在0.5 Hz下收缩。使用IonOptix系统评估力学性能，包括峰值缩短（PS）、至PS时间（TPS）、至90%再强化时间（TR(90)）和最大缩短/再强化速度（+/-dL/dt）。邻苯三酚暴露10分钟（0 ~ 10(-2)M）不影响心脏收缩力学。然而，较长的邻苯三酚暴露时间（1,3,6 h）显著缩短了静息细胞长度，降低了PS和+/- dl /dt，并以时间和浓度依赖性方式延长了TPS和TR90。p38丝裂原活化蛋白（MAP）激酶抑制剂SB203580 （1 μ M）和超氧化物歧化酶（SOD, 500 U/mL）可抑制邻苯三酚（10(-4)M，孵育6 h）诱导的机械缺陷，但邻苯三酚诱导的PS抑制不受SOD的影响。有趣的是，草药抗氧化剂山莨菪碱（10(-7)M）和TMP （10(-7) M）的培养有效地减弱了邻苯三酚诱导的心脏机械缺陷，除了不受TMP影响的PS。我们的数据表明邻苯三酚对心脏收缩有直接的抑制作用，可能是以超氧化物和p38 MAP激酶依赖的方式。抗氧化药物山莨菪碱和TMP可能有助于治疗氧自由基诱导的心肌功能障碍。
Oxygen-derived free radicals have been demonstrated to contribute to the pathogenesis of myocardial dysfunction, although the underlying mechanism remains not fully understood. This study was designed to examine the role of the superoxide generator pyrogallol on cardiac contractile function and possible intervention with herbal medicines anisodamine and tetramethylpyrazine (TMP) on pyrogallol-induced cardiac contractile response. Adult rat ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix system including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), and maximal velocity of shortening/relengthening (+/-dL/dt). A 10-min exposure of pyrogallol (0 to 10(-2) M) did not affect cardiac contractile mechanics. However, longer duration of pyrogallol exposure (1, 3, and 6 h) significantly shortened resting cell length, reduced PS and +/-dL/dt, and prolonged TPS and TR90 in time- and concentration-dependent manners. The pyrogallol (10(-4) M with 6-h incubation)-induced mechanical defects were prevented by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 (1 microM) and superoxide dismutase (SOD, 500 U/mL) with the exception that pyrogallol-induced PS depression was unaffected by SOD. Interestingly, incubation of herbal antioxidants anisodamine (10(-7) M) and TMP (10(-7) M) effectively attenuated the pyrogallol-induced cardiac mechanical defects with the exception of PS unaffected by TMP. Our data demonstrate a direct inhibitory effect of pyrogallol on cardiac contraction, probably in a superoxide- and p38 MAP kinase-dependent manner. The antioxidant medicines anisodamine and TMP may be useful in the treatment of oxygen free radical-induced myocardial dysfunction.