흰쥐에서의 일산화탄소 중독이 뇌에너지 대사 관련물질 함량변화에 미치는 영향

윤재순(Jae Soon Yun),최신규(Shin Kyu Choi) 대한약학회 1989 약학회지 Vol.33 No.3

To predict the influence of carbon monoxide poisonining on cerebral energy metabolism, rats were exposed to 5000ppm environment for 30 minutes. Carboxyhemoglobin(HBCO) saturation rate in this condition was 72% equally in male and female rats. Cerebral cortex in the rats showed lower level of ATP, glucose, creatine phosphate and higher level of lactate, pyruvate by anaerobic glycolysis. As for the levels of ATP, creatine phosphate and glucose, the cerebral cortex contents of them were larger in female rats of estrus than in male rats, whereas there was no difference between sexes in the levels of pyruvate and lactate. According to time passage from CO intoxication, the mode of changes in cerebral energy metabolite contents was similar in both sexes.

뇌내 Norepinephrine함량변화와 Clonazepam의 항경련효과에 미치는 6-Hydroxydopamine의 영향

윤재순(Jae Soon Yun),김영주(Young Joo Kim) 대한약학회 1988 약학회지 Vol.32 No.1

There is evidence that brain norepinephrine may play a role in experimentally induced seizures in animals. Thus the present experiments were undertaken in an attempt to explore the role of brain norepinephrine in anticonvulsant activity of clonazepam. 6-Hydroxydopamine was given to newborn rats and PTZ-induced seizures were tested 70-90 days after birth and the rats were killed for determination of brain norepinephrine 8 days after the seizure test. Depletion of norepinephrine in the rat brain significantly potentiated the PTZ-induced convulsions and antagonized the effect of clonazepam on clonic seizures, tonic seizures and the number of seizures, but the latency to the seizure and the mortality has not been altered. However the 6-hydroxydopamine-induced antagonism of anticonvulsant action was surmountable by increasing the dose of clonazepam. These results show that brain norepinephrine may play an important role in seizure susceptibility as well as in the anticonvulsant activity of clonazepam in rats.

일산화탄소가 뇌내 신경전달물질 및 그 합성효소에 미치는 영향

윤재순(Jae Soon Yun) 대한약학회 1990 약학회지 Vol.34 No.6

We studied the effect of carbon monoxide(CO)-induced bypoxia on monoamine neurotransmitter and their syntheitc enzyme in rat brain. When the rats were acute or chronic intoxicated at CO 5000 ppm for 30 minutes or 2000 ppm for 1 week each 3 hours, dopamine content increased significantly with decreasing of its turnover in striatum and norepinephrine content was diminished in hypothalamus. 5-hydroxytryptamine content was increased significantly and its turnover was decreased both in striatum and hypothalamus. Tyrosine hydroxylase activity was reduced in striatum. These results suggest that inhibition of TH activity in CO-induced hypoxia is owing to lack of oxygen supply threfore NE content is decreased. We suggest that increasing of dopamine and 5-hydroxytryptamine are due to reduction of its turnover.

인삼 사포닌이 일산화탄소중독 및 노화과정에서 생쥐의 뇌신경세포 분포에 미치는 영향

신정희(Jeung Hee Shin),이인란(Ihn Rhan Lee),조금희(Geum Hee Cho),윤재순(Jae Soon Yun) 대한약학회 1992 약학회지 Vol.36 No.3

The effects of ginseng saponins on the distribution of nerve cells in cerebral cortex of carbon monoxide (CO)-intoxicated mice were studied in the young (5~8 weeks) and aged (43~52 weeks) mice. Mice were exposed to 5000ppm of CO for 40 minutes (72% HbCO). After that, nerve cells in motor(area 4), somatosensory(area 3) and visual(area 17) area of cerebral cortex was observed. In young mice, the number of nerve cells in each area was significantly decreased on 1st, 7th and 14th day after CO intoxication. In aged mice, that was also decreased after CO intoxication. Especially the number of the nerve cells in motor and somatosensory area was significantly decreased on lst and 7th day, while that in visual area was decreased only on 1st day. The number of nerve cells in young mice pretreated with ginseng saponins were significantly decreased less on 7th and 14th day than that of untreated mice. The number of nerve cells in each area of normal aged mice was larger than that of normal young mice. The results suggest that CO exposure causes local degeneration or disturbance of nerve cells and delayed neurologic sequelae, while ginseng saponins might play a role of protective action on the nerve cells which were damaged by CO.

실험적 뇌허혈 및 저산소증에 대한 Flunarizine의 약효 뇌장해에 대한 Flunarizine 효능

김은미(Eun Mi Kim),김영진(Young Jin Kim),신정희(Jeoung Hee Shin),윤재순(Jae Soon Yun) 대한약학회 1988 약학회지 Vol.32 No.5

Recent hypothesis suggested that intracellular accumulation of calcium is a common denominator of ischemic celullar damage. Flunarizine, a calcium entry blocker, posses vasodilating properties in cerebral vascular beds and clinically used in circulatory disorders. The present study was designed to evaluate the effect of flunarizine on ischemic and hypoxic brain damage. An ischemic model was made by bilateral carotid artery ligation (BCAL) in Wistar strain rat. Hypoxic model was made by intravenous injection(i.v.) of KCN to rats and mice. In mice, flunarizine not only reduced the mortality of KCN, but also delayed the onset time of convulsion. The contents of ATP, creatine phosphate and glucose, cerebral energy metabolite, decreased 30 minutes after BCAL and KCN i.v., while that of lactate increased. But these variations were suppressed by flunarizine. Furthermore, increase in the dosage of flunarizne generally promoted the recovery of cerebral energy metabolites in hypoxic animals. The results suggest that flunarizine had a protective effect against ischemic and hypoxic brain damage due to its ameliorating action on the cerebral energy metabolism.

일산화탄소 중독이 뇌내 아미노산 신경전달물질 함량변화에 미치는 영향

정민정(Min Jung Jung),박송자(Son Ja Park),이선희(Sun Hee Lee),윤재순(Jae Soon Yun) 대한약학회 1990 약학회지 Vol.34 No.5

To study influence of carbonmonoxide (CO) poisoning on the content of amino acid neurotransmitter in brain, male rat was exposed to CO 5000 ppm for 30 minutes (60-75% HbCO). Aspartic acid and glutamic acid level in the cerebral cortex and aspartic acid level in the striatum were significantly decreased. GABA level in the cerebral cortex was significantly increased after the 30 and 60 minutes of CO intoxication. Taurine level in both the cerebral cortex and the striatum was increased although nonsignificant. Consequently, the CO-induced hypoxia brain showed lower level of excitatory neurotransmitter, aspartic acid and glutamic acid and higher level of inhibitory nelirotransmitter, GABA and taurine. These results suggest that the change in content of amino acid neurotransmitter in the rat brain may be concerned with several CO poisoning symptoms.

Docosahexaenoic acid가 전기충격성 뇌장애 마우스의 기억력 및 Acetylcholine량 변화에 미치는 영향

김문정(Moon Jung Kim),신정희(Jeung Hi Shin),윤재순(Jae Soon Yun) 대한약학회 1995 약학회지 Vol.39 No.3

Electroconvulsive shock (ECS) increases the activity of acetylcholinesterase and decreases in brain acetylcholine levels. A large amount of free fatty acids accumulated in the brain tissue affects cerebral blood flow, brain edema and inflammation and results in brain injury. The present study examined the effect of docosahexaenoic acid (DHA) and D,L-pyroglutamic acid (D,L-PCA) on the learning and memory deficit using the passive avoidance failure technique and on the change of acetylcholine and choline level in the cerebral cortex of ECS-induced mice. The application of ECS (25mA, 0.5 sec) induced a significant decrease in memory function for 30 min. ECS-induced a significant decrease in cortical acetylcholine and choline levels 1 min following the ECS application, which were almost recovered to ECS control level after 30 min. DHA (20mg/kg, i.p.), administered 24 hr before shock, prevented the ECS-induced passive avoidance failure and the decrease of acetylcholine level 1 min following the ECS application. DHA failed to elicit a change in cortical choline level. DHA did not affect memory function and the cortical Ach and choline level of normal mice. The administration of D,L-PCA (500mg/kg, i.p.) increased the effect of DHA on memory function and the change of cortical acetylcholine level of ECS induced mice. These results suggest that DHA treatment may be contributed to the prevention against memory deficit and to the activation of cholinergic system in the ECS induced mice.

인삼 사포닌이 일산화탄소중독 및 노화과정에서 흰쥐의 뇌에너지 대사물 함량 변화에 미치는 영향

신정희(Jeung Hee Shin),최현진(Hyung Jin Choi),강지원(Ji Won Kang),박혜영(Hea Young Park),윤재순(Jae Soon Yun) 大韓藥學會 1992 약학회지 Vol.36 No.3

This study was performed to investigate the effects of ginseng saponins on the cerebral energy metabolite''s contents influenced by carbon monoxide(CO) intoxication. Each experimental group was divided into young (5~8 weeks) and aged (43~52 weeks) rats, and they were exposed to 5,000 ppm CO (72% HbCO) for 30 min. One of the other groups was pretreated with ginseng saponins for 5 days before CO intoxication. The contents of cerebral energy metabolites in cerebral cortex, stratum and hypothalamus were measured. In cerebral cortex of both young and aged rats, the levels of ATP and creatine phosphate were significantly decreased, while those of lactate were significantly increased. There was no difference between the levels of cerebral energy metabolites of young and aged rats. Pretreatment of ginseng saponins before CO intoxication lowered decrease of the levels of cerebral energy metabolites and ATP levels were significantly recovered. On the other hands, contents of lactate in stratum and hypothalamus of young rats were significantly increased and the levels of ATP and creatine phosphate in stratum and hypothalamus were completely recovered at 2 weeks after CO intoxication. The results suggest that ginseng saponins have an ameliorating action against disturbance of the cerebral energy metabolites by CO intoxication.

Eicosapentaenoic acid의 藥理效果에 關한 硏究

尹再順 梨花女子大學校 韓國生活科學硏究院 1984 韓國生活科學硏究院 論叢 Vol.34 No.-

Trienoic prostaglandins의 전구체 Eicosapentaenoic acid(EPA)를 다량 식이로 섭취하면 急性心筋梗症, 動脈硬化를 방지하고 오히려 출혈경향이 있다. 따라서 EPA가 혈압에 미치는 영향을 규명해보고자 EPA 투여후 마취 흰쥐의 혈압을 측정하였다. EPA 200㎎/㎏ 투여시 23∼31%의 혈압 강하작용이 2시간 지속되었고 indomethacin(Ind.) 2㎎/㎏ 5일간 전처리로 EPA에 의한 혈압강하작용이 39.0∼74.0% 억제되었고 H-blocker 전처리로는 69∼89%까지 억제되었다. 또 적출혈관에 대한 수축력을 측정하였다. 흰쥐 흉부 대동맥은 EPA에 의해서 norepinephrine(NE) 의존수축반응곡선을 약간 완화하였고 토끼의 적출상장간막동맥은 EPA 10^-3M 용액에서 NE 의존수축반응곡선을 현저히 억제하였으며 최대수축력이 control의 25%에 불과했다. 또한 Ind. 3X10^-6M 전처리로 EPA 10^-3M 용액에서 NE 3X10^-4M 적용시의 수축반응이 58.3%가 억제되었다. 결론적으로 EPA는 혈압강하작용이 있으며, 이것은 Ind.과 H-blocker로 억제되었고 혈관에 대한 수축작용은 동물종, 혈관부위에 따라 다르다. Epidemiologic studies suggested that dietary intake of eicosapentaenoic acid(EPA), a precursor of trienoic prostaglandins is associated with a low incidence and reduced extent of myocardial infarction and atherosclerosis. The purpose of this study was to investigate the pharmacological effect of EPA on blood pressure and isolated vascular reactivity. EPA was infused directly into femoral vessel of anesthetized rats and carotid arterial blood pressure was measured. Blood pressure of anesthetized rats were observed to be lowered by 23.0∼31.0% and continued for 2 hours by administration of EPA 200㎎/㎏. The hypotensive action induced with EPA was inhibited by 39.0∼74.0% by pretreatment with indomethacin 2㎎/㎏ for 5days. The contractile force to isolated thoracic aorta and superior mesenteric artery from rats and rabbits were measured. When EPA was infused into organ bath with isolated vascular duct, the spiral strips of rat and rabbit thoracic aorta were weakly inhibited and superior mesenteric arterial strips isolated from rabbits were significantly inhibited in response to the contractile effect of norepinephrine (NE). From the above results we conclueded that EPA showed the significant hypotensive response depending on the administerd dosage and inhibited in dose-response to the contractile effect of NE according to animal species and parts of vascular system.

6-Hydroxydopamine이 Clonidine의 抗高血壓 效能에 미치는 影響

尹再順,李恩珠 梨花女子大學校 韓國生活科學硏究院 1986 韓國生活科學硏究院 論叢 Vol.38 No.-

6-Hydroxydopamine(6-OHDA)은 交感神經切除 效果가 있다는 보고가 있어 中樞性抗高血壓藥 clonidine과 삼환계항우울약 desipramine 병용시의 효능변화와 DOCA-salt 처치로 高血壓症發生에 미치는 交感神經의 역활을 검토하고저 6-OHDA을 출생시 투여하여 抗高血壓藥物??효과에 미치는 영향을 관찰하였다. 정상쥐나 DOCA-salt 유발고혈압쥐에서 유의적인 큰 폭으로 나타난 clonidine의 抗高血壓反應은 6-OHDA 처치로 거의 나타나지 않았다. Desipramine 전처치로도 매우 유의적으로 억제되었다. 6-OHDA을 전처치한 쥐는 desipramine 투여에 관계없이 clonidine의 抗高血壓反應이 억제되었다. 또한 6-OHDA 처치한 후 DOCA-salt 투여시의 抗高血壓症도 미약하였다. 이상의 결과에서 6-OHDA, clonidine 및 desipramine은 모두 뇌신경과의 높은 친화력으로 中樞性 抗高血壓症發現이나 억제에 中樞交感神經을 개재하여 큰 영향을 미치며 특히 6-OHDA은 여러 요인의 抗高血壓發生初期의 기전에 중요한 역할을 하는 것으로 나타났다. The effect of neurotoxic compound 6-hydroxydopamine (6-OHDA) on the change in blood pressure by centrally acting agents has been studied in normal and deoxycorticosterone acetate-salt induced hypertensive rats. Administration of clonidine (100㎍ kg^-1 i.v.) lowered the blood pressure in rats. In the case of neonatally 6-OHDA (2×l00mg, 250mg kg^-1 s.c.) treated rats, the antihypertensive effect of clonidine was not shown. And there is significant difference (p<0.01) to be compared with the effect of clonidine alone in normal rats. The hypotensive response of clonidine was reduced markedly by simultaneously administered desipramine (600,㎍ kg^-1 i.v.) in normal and DOCA-salt induced hypertensive rats, but reduced without regard to treatment and untreatment of desipramine in neonatally 6-OHDA treated sympathectomized rats. Administration of 6-OHDA prevented the development of DOCA-salt hypertensive rats. In this hypertensive rats, the hypotensive response of clonidine was significantly reduced by 6-OHDA or desipramine pretreatment. These results suggest that high affinity with central neuron in brain of 6-OHDA, clonidine and desipramine was high significant correlation in development and inhibition of central hypertension mediated central adrenergic neuron.