Coskun C, Avci B, Yalcin M, Yermezler A, Yilmaz M S, Savci V
Department of Medical Pharmacology, Faculty of Medicine, Uludag University, 16059, Bursa, Turkey.
Ir J Med Sci. 2014 Dec;183(4):539-48. doi: 10.1007/s11845-013-1046-3. Epub 2013 Nov 29.
CDP-choline exerts tissue protective effect in several ischemic conditions. Recently we have reported that the drug prevents cardiac arrhythmias and improves survival rate in short-term myocardial ischemia reperfusion in rats.
In the current study, we determined the effect of intravenously administered CDP-choline on myocardial tissue injury induced by 30-min ischemia followed by 3-h reperfusion in anesthetized rats.
Myocardial ischemia was produced by ligature of the left main coronary artery. CDP-choline (100-500 mg/kg) was intravenously injected in the middle of the ischemic period. Cardiovascular parameters were recorded through the experimental period. At the end of the reperfusion period, the hearts of the animals were removed and stained for the investigation of tissue necrosis and apoptosis. The infarct size was evaluated as the ratio of the infarct area to the risk area. Apoptotic activation was assessed by TUNEL assay. Also the blood samples of rats were collected for the measurement of M30-M65, ADMA, homocysteine, and lactate levels.
Ischemia/reperfusion caused serious injury in myocardium, increased blood ADMA and lactate levels without influencing other parameters. CDP-choline significantly reduced the infarct size and the number of apoptotic cells in the risk area. Blood pressure increased after CDP-choline injection; however, it returned back to the basal levels before the onset of reperfusion. CDP-choline failed to alter any other measured parameters.
The present results demonstrate that intravenously administered CDP-choline is able to protect myocardium from injury induced by long-term coronary occlusion-reperfusion in rats. The inhibition of apoptosis by the drug may contribute to its protective effect. But neither the increase in blood pressure in response to CDP-choline injection nor changes in plasma ADMA concentration appear to mediate the attenuation of the myocardial injury.
胞磷胆碱在多种缺血情况下发挥组织保护作用。最近我们报道该药物可预防大鼠短期心肌缺血再灌注时的心律失常并提高存活率。
在本研究中，我们确定了静脉注射胞磷胆碱对麻醉大鼠30分钟缺血后再灌注3小时所致心肌组织损伤的影响。
通过结扎左冠状动脉主干造成心肌缺血。在缺血期中期静脉注射胞磷胆碱（100 - 500毫克/千克）。在整个实验过程中记录心血管参数。在再灌注期结束时，取出动物心脏并进行染色，以研究组织坏死和凋亡情况。梗死面积以梗死区域与危险区域的比值来评估。通过TUNEL法评估凋亡激活情况。同时收集大鼠血液样本以测量M30 - M65、不对称二甲基精氨酸（ADMA）、同型半胱氨酸和乳酸水平。
缺血/再灌注导致心肌严重损伤，血液中ADMA和乳酸水平升高，而其他参数未受影响。胞磷胆碱显著减小梗死面积以及危险区域内凋亡细胞的数量。注射胞磷胆碱后血压升高；然而，在再灌注开始前又恢复到基础水平。胞磷胆碱未能改变任何其他测量参数。
目前的结果表明，静脉注射胞磷胆碱能够保护大鼠心肌免受长期冠状动脉闭塞 - 再灌注所致的损伤。该药物对凋亡的抑制作用可能有助于其保护作用。但是，注射胞磷胆碱后血压的升高以及血浆ADMA浓度的变化似乎均未介导心肌损伤的减轻。
