Barrington P L, Soons K R, Rosenberg P
Toxicon. 1986;24(11-12):1107-16. doi: 10.1016/0041-0101(86)90137-6.
The basic phospholipase A2 from Naja nigricollis snake venom is cardiotoxic, causing decreased contractility and arrhythmias at concentrations which induce low levels of phospholipid hydrolysis. Cardiac tissue has a high content of arachidonic acid at the sn-2 position of the major membrane phospholipids, thus increased prostaglandin synthesis might contribute to the cardiotoxic effects of N. nigricollis phospholipase A2. Intracellular action potentials and cardiac contractility were monitored in the isolated right ventricular wall of the rat heart exposed for 1 hr to N. nigricollis phospholipase A2, with or without indomethacin, or to arachidonic acid. The tissues were homogenized, prostaglandins extracted and the 6-keto PGF1 alpha and PGE2 content of the hearts determined. The physiologic effects and prostaglandin content of hearts treated with N. nigricollis phospholipase A2 were not altered by indomethacin nor mimicked by concentrations of arachidonic acid comparable to that present in N. nigricollis phospholipase A2-treated tissue. These results support our previous suggestion that exogenously applied N. nigricollis phospholipase A2 causes cardiotoxic effects by a mechanism that is independent of phospholipid hydrolysis.
来自黑颈眼镜蛇蛇毒的基本磷脂酶A2具有心脏毒性，在诱导低水平磷脂水解的浓度下会导致收缩性降低和心律失常。心脏组织在主要膜磷脂的sn-2位置含有高含量的花生四烯酸，因此前列腺素合成增加可能有助于黑颈眼镜蛇磷脂酶A2的心脏毒性作用。在离体大鼠心脏的右心室壁中监测细胞内动作电位和心脏收缩性，该右心室壁暴露于黑颈眼镜蛇磷脂酶A2 1小时，同时有或没有吲哚美辛，或暴露于花生四烯酸。将组织匀浆，提取前列腺素并测定心脏中6-酮-PGF1α和PGE2的含量。用吲哚美辛处理黑颈眼镜蛇磷脂酶A2的心脏的生理效应和前列腺素含量没有改变，与黑颈眼镜蛇磷脂酶A2处理的组织中存在的花生四烯酸浓度相当的花生四烯酸浓度也不能模拟这些效应。这些结果支持了我们之前的观点，即外源性应用黑颈眼镜蛇磷脂酶A2通过一种独立于磷脂水解的机制引起心脏毒性作用。
