赛庚啶对离体大鼠心脏缺钙/复钙损伤(钙反常)的保护作用

离体大鼠心脏经无钙灌流(灌流液为不含Ca²⁺的K-H液,通以95%O₂和5%CO₂的混合气体)5min后,用正常K-H液进行复钙灌流20min,可导致心肌细胞内酶(CPK,LDH)及蛋白的大量漏出,心脏变苍白,甚至出现心脏挛缩,心肌组织抗氧自由基酶(SOD,GSH-Px)活性明显降低,但MDA含量无明显改变。赛庚啶(2.5～5μmol/L)能明显减少心脏Ca²⁺反常时心肌组织内酶及蛋白的漏出,显著保护心肌组织抗氧自由基酶的活性。

PROTECTIVE EFFECTS OF CYPROHEPTADINE ON CALCIUM PARADOX IN ISOLATED RAT HEARTS

The protective effects of cyproheptadine, an antiserotonin-antihistaminic agent with calcium channel blocker activity, on calcium paradox in isolated Langendorff's heart in rats were studied. After a 5 min of calcium-free perfusion [standard Krebs-Henseleit (K-H) buffer without calcium, gassed with 95% O2 and 5% CO2] followed by a 20 min of normal K-H buffer (Ca2+ 2.5 mmol/L) perfusion, extensive and rapid myocardial injury was observed: release of massive cellular enzymes such as lactic dehydrogenase (LDH) and creatine phosphokinase (CPK), significant decrease of myocardial anti-oxygen free radical enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities but no obvious change of myocardial lipid peroxides such as malondialdehyde (MDA) content was observed. The loss of normal colour and mechanical activity, even contracture, was also observed in the injured hearts. Cyproheptadine (2.5-5 mumol/L) was shown to effectively antagonize the damage. The results suggest that the protective effects of cyproheptadine on the calcium paradox may be related to its actions of blocking calcium channel, protecting anti-oxygen free radical enzymes and scavenging oxygen free radicals in the myocardial tissues.