PROTECTIVE ACTIVITY OF THE SPIN TRAP TERT-BUTYL-ALPHA-PHENYL NITRONE (PBN) IN REPERFUSED RAT-HEART
PROTECTIVE ACTIVITY OF THE SPIN TRAP TERT-BUTYL-ALPHA-PHENYL NITRONE (PBN) IN REPERFUSED RAT-HEART
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DOI：
10.1016/0022-2828(92)93192-m
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发表时间：
1992-04-01
影响因子：
5
通讯作者：
PICCININI, F
中科院分区：
文献类型：
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作者：
BRADAMANTE, S;MONTI, E;PICCININI, F
本研究的目的是探讨自由基在心肌缺血再灌注损伤中是否起因果作用。为此，我们观察了自旋捕获化合物在能够与自由基反应的浓度下使用时是否保护心脏。亲脂性自旋陷阱α-苯基-叔丁基硝酮(PbN)被肌钙石吸收而被使用。按两种方案造成大鼠离体心缺血模型：模型A=零流量缺血30min，再灌流30min；模型B=低流量缺血60min(含氮饱和)，再灌流30min。治疗组在此基础上加用5.0mMPBN，连续给药。在整个实验过程中测量了以下参数：收缩性能(RPP)、冠脉流量(CF)、CPK、磷酸肌酸(PCr)、三磷酸腺苷(ATP)、无机磷(PI)、细胞内pH(Phi)。“模型A”所获得的病理较模型B更严重，且部分不可逆。在“模型A”缺血期，心肌的收缩能力、Pcr和ATP降至接近于零；在最初的复流过程中，CPK上升了约13倍，Pip上升了2.5倍，而pH降至6.1。在再灌流过程中，Pcr、Pi和pHi部分恢复，RPP和ATP未见增加，PBN治疗后Pcr和CPK显著改善，其余指标无明显变化。在缺血期间，“B型”心脏的收缩能力下降到接近零，PCr下降到35%，ATP下降到50%；CPK上升7倍，Pi1.5倍；PHi没有改变。再灌流期间，除PI外，其余参数均部分恢复。PBN在所有测试参数上都表现出明显的保护活性，接近正常值。目前的研究结果表明，亲脂性自旋陷阱PBN对心脏缺血/再灌注损伤具有部分保护作用，从而证实了自由基在这一病理过程中的作用；组织中药物的持续负荷可能是获得保护作用的重要因素。
The aim of this work was to ascettain whether free radicals play a causal role in the injury occurring in myocardial ischemia and reperfusion. To this purpose we observed whether spin-trapping compounds protect the heart when used at a concentration capable of reacting with free radicals. The lipophilic spin trap α-phenyl-t-butyl nitrone (PBN) was used because it is taken up by the myocites. Isolated Langendorff rat hearts were subjected to ischemia according to two schemes: “Model A” = 30 min zero-flow ischemia followed by 30 min reperfusion; “Model B” = 60 min of low-flow ischemia (10% of the individual value; N2saturated) followed by 30 min reperfusion. Treated groups received in addition 5.0 mmPBN which was supplied continuously. The following parameters were measured throughout the experiment: contractile performance (RPP); coronary flow (CF); CPK; phosphocreatine (PCr), ATP, inorganic phosphate (Pi), intracellular pH (pHi). The pathology obtained by “Model A” is more severe than that of Model B, and partly irreversible. During the ischemic phase in “Model A”, contractility, PCr and ATP dropped to near zero; during initial reflow CPK rose about 13-fold andPirose 2.5-fold, while pHidecreased to 6.1. During reperfusion, a partial recovery of PCr,Piand pHiwas observed, while RPP and ATP did not increase; PBN treatment improved significantly PCr and CPK, while the other parameters were unaffected. During ischemia, “Model B” hearts showed a drop of contractility to near zero, of PCr to 35%, of ATP to 50%; CPK rose 7-fold and Pi1.5-fold; pHiwas not modified. During reperfusion, all parameters recovered in part, with exception ofPi. PBN developed a marked protective activity on all tested parameters, which gained a nearly normal value. The results of the present investigations show that the lipophilic spin trap PBN partly protects the heart from the ischemia/reperfusion injury, thus confirming that free radicals play a causal role in this pathology; the continuous loading of the tissue with the drug can be an important factor for obtaining the protective effect.