Briede Janïna, Duburs Gunárs
Latvian Institute of Organic Synthesis, Latvial.
Cell Biochem Funct. 2007 Mar-Apr;25(2):203-10. doi: 10.1002/cbf.1318.
Diabetes mellitus is accompanied by several cardiovascular complications including atherosclerosis, cerebral ischaemia and stroke. We examined the neuroprotective effect of a 1,4-dihydropyridine derivative cerebrocrast (C, a new antidiabetic agent, synthesized in the Latvian Institute of Organic Synthesis) on the level of ATP in the brain, and on changes of the EEG and ECG, as well as blood pressure parameters in anaesthetized Wistar male rats before and during 10-min occlusion of both common carotid arteries. Cerebrocrast was administered i.v. at doses of 1.0 and 10 microg/kg in the v. femoralis 20 min prior to ischaemia. After 10-min ischaemia animals were decapitated and the brain was immediately frozen in liquid nitrogen and subsequently used for analysis of changes of ATP contention. Cerebrocrast, administered at doses of 1.0 and 10 microg/kg 20 min prior to occlusion of both common carotid arteries, completely prevented a fall in the ATP content of brain compared with the control rats. In control rats the content of ATP in brain during ischaemia decreased from 2.77 +/- 0.22 (basal level) to 1.74 +/- 0.20 micromol/g as a result of ischaemia. By administration of cerebrocrast 20 min before occlusion of the arteries, the content of ATP in the brain remained at the level of preischaemia (1.0 microg/kg C + ischaemia 2.82 +/- 0.36; 10 microg/kg C + ischaemia 2.42 +/- 0.22 micromol/g). Analysis of EEG parameters both before and during 10 min of occlusion showed that at a C dose of 1.0 microg/kg before occlusion produced a regular alpha rhythm during ischaemia and prevented cerebral bioelectric activity from significant changes. The depression of basal rhythm was observed at a C dose of 10 microg/kg during ischaemia in two rats out of six as well as an increase in the ECG ST segment above the isoelectric line. Blood pressure was decreased by about 10-20 mm Hg. We propose that pretreatment of rats with cerebrocrast at doses of 1.0 or 10 microg/kg 20 min prior to ischaemia can prevent ischaemic damage of rat brain, maintain necessary energy consumption, promote ATP production in brain cells, and prevent significant changes in EEG and ECG parameters. These properties are important in diabetes mellitus and its evoked cardiovascular complications as stroke, ischaemia, etc.
糖尿病伴有多种心血管并发症，包括动脉粥样硬化、脑缺血和中风。我们研究了一种1,4 - 二氢吡啶衍生物脑复康（C，一种在拉脱维亚有机合成研究所合成的新型抗糖尿病药物）对麻醉的雄性Wistar大鼠在双侧颈总动脉闭塞10分钟之前及期间大脑中ATP水平、脑电图（EEG）和心电图（ECG）变化以及血压参数的神经保护作用。在缺血前20分钟，通过股静脉以1.0和10微克/千克的剂量静脉注射脑复康。缺血10分钟后，将动物断头，大脑立即在液氮中冷冻，随后用于分析ATP含量的变化。在双侧颈总动脉闭塞前20分钟给予1.0和10微克/千克剂量的脑复康，与对照大鼠相比，完全防止了大脑中ATP含量的下降。在对照大鼠中，缺血期间大脑中的ATP含量由于缺血从2.77±0.22（基础水平）降至1.74±0.20微摩尔/克。通过在动脉闭塞前20分钟给予脑复康，大脑中的ATP含量保持在缺血前水平（1.0微克/千克C + 缺血2.82±0.36；10微克/千克C + 缺血2.42±0.22微摩尔/克）。对闭塞10分钟之前及期间的EEG参数分析表明，在闭塞前给予1.0微克/千克剂量的C在缺血期间产生了规则的α节律，并防止了大脑生物电活动的显著变化。在缺血期间，6只大鼠中有2只在给予10微克/千克剂量的C时观察到基础节律的抑制以及心电图ST段高于等电位线的增加。血压下降了约10 - 20毫米汞柱。我们提出，在缺血前20分钟用1.0或10微克/千克剂量的脑复康预处理大鼠可以预防大鼠脑缺血损伤，维持必要的能量消耗，促进脑细胞中的ATP产生，并防止EEG和ECG参数的显著变化。这些特性在糖尿病及其引发的心血管并发症如中风、缺血等方面具有重要意义。
