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I. 서론 6
II. 실험방법 8
1. 실험방법 8
2. 약물 및 투여 8
3. 실험군의 구분 9
4. 양측 총경동맥의 영구 폐쇄 9
5. Morris 수중미로에 의한 학습 훈련 10
6. Morris 수중미로에 의한 공간기억력 측정 11
7. 뇌조직의 처리 12
8. SOD와 MDA의 측정 12
9. 뇌조직의 염색 13
10. 뇌조직의 관찰 14
11. 통계처리 14
III. 결과 15
1. 도피대 회피시간의 변화 15
2. 수중미로 구역별 수영시간의 변화 18
3. 도피대를 찾아간 횟수 및 처음으로 찾아간 시간의 변화 21
4. 도피대 주변에서 수영한 시간비율의 변화 23
5. 기억유지 점수의 변화 25
6. 뇌조직 superoxide dismutase 활성도의 변화 27
7. 뇌조직 malondialdehyde 농도의 변화 29
8. 해마 조직의 4-hydroxynoneral 발현 변화 31
9. 해마 조직의 8-hydroxy-2'-deoxyguanosine 발현 변화 34
10. GSTpi와 4HNE 및 8-OHdG의 발현 37
IV. 고찰 39
V. 결론 44
참고문헌 46
Abstract 54
Fig. 1. Chemical structure of luteolin. 8
Fig. 2. Schematic diagram of platform position in the swimming pool (A) and computerized grid design used in the retention test (B). Discrete zones are labeled with letters. zone A representing the... 11
Fig. 3. Effect of luteolin (LUT) on escape latency in the acquisition training trials. LUT treatment significantly shortened the escape latency on the 3rd day compared to the Control group.... 17
Fig. 4. Representative swimming tracts in the retention test of the Sham, Control. and LUT groups. The control group was subjected to permanent bilateral common carotid artery occlusion (pBCAO).... 19
Fig. 5. Effect of luteolin (LUT) on the time spent in discrete zones. LUT treatment significantly prolonged the swimming time spent in zone B, while the time spent in zone G was significantly shortened... 20
Fig. 6. Effects of lutealin (LUT) on the number of target heading and the time for the 1st target heading. LUT treatment did not show a significant change in the number of target heading, while the time for... 22
Fig. 7. Effect of luteolin (LUT) on the % swim in the target area. LUT treatment significantly increased the % swim in the target area compared to the Control group.... 24
Fig. 8. Effect of luteolin (LUT) on the memory score in the retention test. LUT treatment significantly increased the memory score compared to the Control group.... 26
Fig. 9. Effect of luteolin (LUT) on superoxide dismutase (SOD) activities in the cerebral cortex and the hippocampus. LUT treatment significantly attenuated the reduction of SOD activity in the cerebral ... 28
Fig. 10. Effect of luteolin (LUT) on malondialdehyde (MDA) levels in the cerebral cortex and the hippocampus. LUT treatment significantly attenuated the increase of MDA level in the hippocampus compared to... 30
Fig. 11. Representative photographs of the 4HNE immuno-stained hippocampus of the Sham, Control. and LUT groups. The control group was subjected to permanent bilateral common carotid artery occlusion... 32
Fig. 12. Effect of luteolin (LUT) on the 4-hydroxynonenal (4HNE)-expressing cells in the hippocampus. LUT treatment significantly attenuated the increase in optical density of the 4HNE-expressing cells... 33
Fig. 13. Representative photographs of the 8-OHdG immuno-stained hippocampus of the Sham, Control, and LUT groups. The control group was subjected to permanent bilateral common carotid artery occlusion... 35
Fig. 14. Effect of luteolin (LUT) on the 8-hydroxy-2'-deoxyguanosine (8-OHdG)-expressing cells in the hippocampus. LUT treatment significantly attenuated the increase in optical density of the... 36
Fig. 15. Representative photographs of double-immunofluorescent labeling of GSTpi-expressing region with 4HNE-expressing cells and 8-OHdG-expressing cells in the hippocampus.... 38
초록보기 더보기
Luteolin (LUT) is a flavonoid compound in Flos Lonicerae Japonicae and Scutellaris baicalensis Georgi and has a wide range of anti-oxidative, anti-inflammatory, and neuroprotective effects. This study was investigated the effects of LUT on learning and memory impairment induced by permanent bilateral common carotid artery occlusion (pBCAO) in rats. LUT was administered orally once a day (30 mg/kg) for 28 days starting at 4 weeks after the pBCAO. The acquisition of learning and the retention of memory were tested on 9th week after the pBCAO using the Morris water maze. In addition, effects of AST on oxidative damage were evaluated with levels of superoxide dismutase (SOD) and malondialdehyde (MDA) and expressions of 4-hydroxynonenal (4HNE) and 8-hydroxy-2'-deoxy-guanosine (8-OHdG) in the brain tissue of rat which was performed the Morris water maze test.
The results are as followings；
1. LUT significantly shortened the escape latencies on the 3rd day of acquisition training trials.
2. LUT significantly prolonged the swimming time spent in the target and peri-target zones and significantly reduced the swimming time spent in zones far from the target.
3. LUT significantly shortened the time for the 1st target heading in the retention test.
4. LUT significantly increased the % swim in the targer area in the retention test.
5. LUT significantly increased the memory score in the retention test,
6. LUT significantly increased the down-regulated SOD level in the cerebral cortex.
7. LUT significantly attenuated the up-regulation of MDA level in the hippocampus.
8. LUT significantly attenuated the up-regulation of 4HNE expression in the CA1 of hippocampus.
9. LUT significantly attenuated the up-regulation of 8-OHdG expression in the CA1 of hippocampus.
The results suggest that LUT exert ameliorating effect on memory impairment through inhibition of oxidative damage in brain tissue and may be a beneficial medicinal compound to treat cognitive impairment and neurodegenerative diseases.
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