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배양 마우스 신경세포에서 phenylpropanoid 유도체의 NMDA 및 산소/포도당 결핍 유발 손상에 대한 방어효과
위명복 제주대학교 생명과학연구소 1998 제주생명과학연구 Vol.1 No.-
The phenylpropanoids, naturally occurring compounds, have been known to contain the aromatic ring to which a three-carbon side chain is attached and various pharmacological actions. In our previous studies, we demonstrated that eugenol, one of the phenylpropanoid compounds has the neuroprotective effects in the in vitro and in vivo ischemia models. In this study, we studied whether other phenylpropanoid derivatives, myristicin, 4-allylanisole, α-asarone, and β-asarone have the similar neuroprotective action on N-methyl-D-aspartate (NMDA) or oxygen/glucose deprivation (OGD)-induced neurotoxicity in cultured mixed cortical Neurons. Between the 30μM and 300μM concentration, myristicim, 4-allyanisole, α-asarone reced LDH release by 9-95%, 0-88%, 14-77% and 15-98% against the NMDA(300 μM)-induced acute neurotoxicity, respectively. However, in the OGD paradyme, only both 4-allylanisole and α-asarone, significantly(p<0.05) showed 27% and 30% neuroprotective effect at the maximal concentration (300μM),respectively. These results suggest that phenylpropanoid derivatives may offer a helpful contribution for the improvement of the glutamate-related neurodegenerative diseases.
위명복,송동근,강병태,정전섭,최연식,박준형,김영희,Wie, Myung-Bok,Song, Dong-Keun,Kang, Byung-Tae,Jung, Jun-Sub,Choi, Yeun-Sik,Park, Joon-Hyoung,Kim, Yung-Hi The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.1
We studied changes in the hypothalamic norepinephrine(NE) metabolism in streptozotocin (STZ)-induced diabetic rats by measuring basal NE levels, turnover rate of NE, and in vivo tyrosine hydroxylase activities. Basal NE level did not change significantly upto 4 weeks after the establishment of diabetes with STZ(60 mg/kg, iv). But turnover rate of NE decreased to 62% of control rate(P<0.01), and in vivo tyrosine hydroxylase activities decreased to 32% of control level(P<0.05) at one week of diabetes. From these results, we concluded that, of the three parameters measured, in vive tyrosine hydroxylase activity is the most sensitive index of altered hypothalamic NE metabloism in STZ-induced diabetic rats. Streptozotocin(STZ)-유발 당뇨쥐에서 시상하부의 norepinephrine(NE) 대사를 기초 NE 함량, NE 교체율, in vivo tyrosine hydroxylase(TH) 활성을 그 지표로 하여 조사하였다. STZ (60 mg/kg, iv)로 당뇨를 유발한 후 4주까지 기초 NE 함량은 유의한 변화가 없었다. 그러나 당뇨유발 후 1주째에 측정한 NE 교체율은 대조치의 62%(p<0.01), in vivo TH 활성은 대조치의 34% (p<0.05)로 감소하였다. 이상의 결과로 본 실험에서 측정한 NE 대사의 세 지표 중에서 in vivo TH 활성이 STZ-유발 당뇨쥐의 시상하부 NE 대사의 변화를 가장 민감하게 반영하였다.
생쥐 피질세포배양에서 Free Radical 유발 신경손상에 대한 손바닥선인장 및 삼백초의 보호효과
위명복(Myung Bok Wie) 대한약학회 2000 약학회지 Vol.44 No.6
The author examined whether the methanol extracts of Opuntia ficus-indica fruit and Saururus chinensis have the inhibitory action on xanthine/xanthine oxidase (X/XO)-, FeCl2/ascorbic acid- and arachidonic acid-induced neurotoxicity in mouse cortical cell cultures. The methanol extracts (10mcg/ml~1mg/ml) of Opuntia ficus-indica and Saururus chinensis were exhibited 53-89% and 48-100% inhibitory action on X/XO-induced neurotoxicity, respectively. At the range of same concentration, both extracts also attenuated the FeCl2/ascorbic acid-induced neurotoxicity by 35-100% and 15-98%, respectively. In arachidoiic acid neurotoxicity, the methanol extracts (1mg/ml) of Opuntia ficus-indica and Saururus chinensis reduced neuronal injury by 22% and 38%, respectively. These results suggest that Opuntia ficus-indica fruit and Saururus chinensis may contribute the neuroprotection in certain free radical-mediated neuronal injury.
Streptozotocin-유발 당뇨쥐의 시상하부에서 Norepinephrine 함량은 정상이나 In vivo Tyrosine Hydroxylase 활성은 감소함
위명복(Myung-Bok Wie),송동근(Dong-Keun Song),강병태(Byung-Tae Kang),정전섭(Jun-Sub Jung),최연식(Yeun-Sik Choi),박준형(Joon-Hyoung Park),김영희(Yung-Hi Kim) 대한약리학회 1991 대한약리학잡지 Vol.27 No.1
Streptozotocin(STZ)-유발 당뇨쥐에서 시상하부의 norepinephrine(NE) 대사를 기초 NE 함량, NE 교체율, in vivo tyrosine hydroxylase(TH) 활성을 그 지표로 하여 조사하였다. STZ (60 mg/kg, iv)로 당뇨를 유발한 후 4주까지 기초 NE 함량은 유의한 변화가 없었다. 그러나 당뇨유발 후 1주째에 측정한 NE 교체율은 대조치의 62%(p<0.01), in vivo TH 활성은 대조치의 34% (p<0.05)로 감소하였다. 이상의 결과로 본 실험에서 측정한 NE 대사의 세 지표 중에서 in vivo TH 활성이 STZ-유발 당뇨쥐의 시상하부 NE 대사의 변화를 가장 민감하게 반영하였다. We studied changes in the hypothalamic norepinephrine(NE) metabolism in streptozotocin (STZ)-induced diabetic rats by measuring basal NE levels, turnover rate of NE, and in vivo tyrosine hydroxylase activities. Basal NE level did not change significantly upto 4 weeks after the establishment of diabetes with STZ(60 mg/kg, iv). But turnover rate of NE decreased to 62% of control rate(P<0.01), and in vivo tyrosine hydroxylase activities decreased to 32% of control level(P<0.05) at one week of diabetes. From these results, we concluded that, of the three parameters measured, in vive tyrosine hydroxylase activity is the most sensitive index of altered hypothalamic NE metabloism in STZ-induced diabetic rats.
몇가지 정유가 Rat의 위액분비 및 비둘기의 위운동에 미치는 영향
魏明復,朴駿瀅 慶北大學校出版部 1987 慶北大農學誌 Vol.5 No.-
Anethole, eugenol, isoeugenol, safrole and isosafrole are ingredients of refined oils which are obtained from some plants and their chemical structures are very similar. They are mainly used as a flavoring agent, food additive, dental analgesics and for many drugs. But, there is no report about their effect on gastric secretion and gastric motility. To examine the effect of anethole, eugenol. isoeugenol, safrole and isosafrole on gastric secretion in rats and gastric motility in pigeons, this paper was investigated. The results were as follows ; 1. All of 5 essential oils showed significant inhibitory effect compared with control group on gastric secretion at the rate of 1.00 ㎖l / 100 g, 0.50 ㎖/ 100 g B.W. in the rat. 2. Eugenol, isoeugenol and isosafrole showed significant inhibitory effect on gastric secretion at the rate of 0.25㎖ / 100 g B.W. in the rat. 3. Isosafrole showed the most inhibitory effect on gastric secretion in 5 essential oils. 4. All of 5 essential oils, in a more or less degree, showed temporary inhibitory effect on gastric motility in the pigeon. 5. In conclusion, all of 5 essential oils showed inhibitory action on gastric secretion in the rat and gastric motility in the pigeon.
Glutamate-Induced Serotonin Depletion in Fetal Rat Brainstem Cultures
박상욱,위명복,송동근,김용식,김영희,Park, Sang-Wook,Wie, Myung-Bok,Song, Dong-Keun,Kim, Yong-Sik,Kim, Yung-Hi The Korean Society of Pharmacology 1993 대한약리학잡지 Vol.29 No.2
흰쥐태 뇌간의 세포를 배양하여 glutamate에 6시간까지 노출시 glutamate의 농도 및 노출 시간에 의존적으로 세포내 5-HT 및 5-HIAA의 함량이 감소하였고, 배양액으로 LDH의 유출이 증가하였다. Tetrodotoxin은 glutamate의 작용을 차단하지 못하였다. NMDA 수용체 통로 봉쇄제인 MK-801에 의해 glutamate의 작용이 효과적으로 차단되었고, non-NMDA 길항제인 CNQX는 효과가 없었으므로, serotonin 신경세포에 대한 glutamate의 작용은 NMDA 수용체의 자극에 의한 것으로 사료된다. Exposure of dissociated cultures from fetal rat brainstem to glutamate for upto 6 h decreased cellular contents of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in a concentration- and time-dependent manner. In addition, glutamate induced lactate dehydrogenase leakage. Tetrodotoxin did not block the effects induced by glutamate. MK-801 $(1{\mu}M)$, an N-methyl-D-aspartate (NMDA) channel blocker, but not 6-cyano-2,3-dihydroxy-7-nitro-quinoxazoline $(CNQX;\;3{\mu}M)$, a non-NMDA receptor antagonist, blocked glutamate-induced effects, indicating that these glutamate-induced responses are mediated through NMDA receptors.
송동근,위명복,박찬웅,김영희,Song, Dong-Keun,Wie, Myung-Bok,Park, Chan-Woong,Kim, Yung-Hi The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.1
쥐(태령 14일) 뇌간 세포배양에서 발달과정에 따른 Tyrosine hydroxylase(TH) 활성 및 dopamine의 양적 증가를 전기화학 HPLC를 이용하여 측정하였다. TH 활성 및 dopamine의 양은 배양 7일까지 점차 증가하였다. 배양 7일째에 여러 약물들의 dopamine 대사에 대한 영향을 조사하였다. TH 억제제인 ${\alpha}-methyl-p-tyrosine$ 및 aromatic amiono acid decarboxylase 억제제인 NSD-1015는 효과적으로 dopamine을 고갈시켰다. Dopamine은 reserpine에 의해 고갈되었고, parglyine에 의해 증가되었다. 일주일 배양한 세포의 배양액에 tetrodotoxin$(0.1\;{\mu}M$)을 7일간 투여하였을 때 TH 활성은 현저히 감소하였다. 이상의 결과들은 배양세포의 dopamine 대사가 뇌 dopamine 대사를 충실히 반영함을 나타낸다. 뇌간 세포의 배양에서 HPLC-전기화학검출을 이용한 TH 활성 및 dopamine의 측정은 중추 dopamine계의 약리 및 독성 연구에 유용하리라 사료된다. We measured the developmental increase of tyrosine hydroxylase(TH) activity and dopamine content with high performance liquid chromatography with electrochemical detection(HPLC-EC) in dissociated cultures of fetal rat brainstem(E14). TH activity and dopamine content increased progressively upto 7 days in vitro, when the effects of various drugs on the dopamine contents were studied. ${\alpha}-Methyl-p-tyrosine$, a TH inhibitor and NSD-1015, an inhibitor of aromatic amiono acid decarboxylase effectively depleted dopamine contents. Dopamine contents were depleted by reserpine and increased by pargyline. When cultures grown for 1 week in control medium were then exposed to tetrodotoxin$(0.1\;{\mu}M$) for 7 days, exposure to tetrodotoxin markedly decreased TH activity. All the above results indicate that dopamine metabolism in the cultered cells reflect reliably the property of brain dopamine metabolism. We suggest that measuring TH activity and dopamine content in brainstem culture with HPLC-EC can be useful tool in the study of pharmacology as well as toxicology of the central dopaminergic system.