順氣活血湯의 腦虛血 抑制效果에 관한 實驗的 硏究
(The) Experimental study of Sunkihwalhyul-Tang against inhibitive effects on the brain ischemia in rats
초록/요약
This Study was designed to investigate the effect of Sunkihwalhyul -Tang extract(SHT) on the change of cerebral hemodynamics〔regional cerebral blood flow(rCBF), pial arterial diameter(PAD) and mean arterial blood pressure(MABP)〕in normal and cerebral ischemic rats, and further to determine the mechanisms of action of SHT on hemodynamics. In addition, this study was designed to investigate whether SHT inhibits lactate dehydrogenase(LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows ; 1. SHT significantly increased rCBF and PAD in a dose-dependent manner, but MABP was not changed by injecting SHT. These results suggest that SHT significantly increases rCBF by dilating PAD. 2. The SHT-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin(IDN, 1 ㎎/㎏, i.p.), an inhibitor of cyclooxygenase and methylene blue(MTB, 10 ㎍/㎏, i.p.), an inhibitor of guanylate cyclase. 3. The SHT-induced dilation in PAD was significantly inhibited by pretreatment with IDN and MTB. 4. The SHT-induced some increase in MABP was significantly increased by pretreatment with IDN. These results suggest that the mechanism of action of SHT is mediated by guanylate cyclase. 5. Both rCBF and PAD were significantly and stably increased by SHT(10 ㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. 6. SHT significantly inhibited LDH activity in neuronal cells. These results suggest that SHT prevents the neuronal death. 7. In cytokine production in the serum drawn from femoral artery 1 hr after middle cerebral arterial occlusion, sample group showed significantly decreased production of IL-1β production, decreased production of TNF-α and increased production of IL-10 compared with control group. 8. In cytokine production in the serum drawn from femoral artery 1 hr after reperfusion, sample group showed significantly decreased production of IL-1β and TNF-α as well as significantly increased production of IL-10 compared with control group. These results suggest that SHT mediated by guanylate cyclase has inhibitive effect on the brain damage by inhibiting LDH activity, IL-1β and TNF-α production, and by accelerating IL-10 production. The present author thinks that SHT has an anti-ischemic effects through the improvement of cerebral hemodynamics and inhibitive effects on the brain damage.
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目次
ABSTRACT = i
Ⅰ. 緖論 = 1
Ⅱ. 材料 및 方法 = 3
1. 재료 = 3
1) 동물 = 3
2) 약재 = 3
2. 방법 = 4
1) 검액의 제조 = 4
2) 정상 흰쥐의 뇌혈류역학 변화 관찰 = 5
3) 정상 흰쥐의 뇌혈류역학 변화에 미치는 기전 관찰 = 7
4) 뇌허혈 병태 모델의 뇌혈류역학 변동에 미치는 개선 효과 관찰 = 7
5) 생쥐의 신경 세포내 lactate dehydrogenase 활성도 측정 = 8
6) 뇌허혈 병태 모델의 혈청내 사이토카인 생성능 측정 = 9
3. 통계처리 = 11
Ⅲ. 實驗成績 = 12
1. SHT가 정상 흰쥐의 뇌혈류역학에 미치는 효과 = 12
2. SHT 투여로 변화된 정상 흰쥐의 뇌혈류역학 작용기전 관찰 = 14
1) SHT 투여로 변화된 정상 흰쥐의 rCBF 작용기전 관찰 = 14
2) SHT 투여로 변화된 정상 흰쥐의 PAD 작용기전 관찰 = 16
3) SHT 투여로 변화된 정상 흰쥐의 MABP 작용기전 관찰 = 18
3. SHT가 뇌허혈 병태 모델의 생리학적 변수에 미치는 영향 = 20
4. SHT가 뇌허혈 병태 모델의 뇌혈류역학 변동에 미치는 개선 효과 = 21
1) SHT가 rCBF 변동에 미치는 개선 효과 = 21
2) SHT가 PAD 변동에 미치는 개선 효과 = 23
5. SHT가 생쥐의 신경 세포의 LDH 활성도에 미치는 효과 = 25
6. SHT가 뇌허혈 병태 모델의 혈청에서 생산되는 사이토카인 양에 미치는 효과 = 27
1) MCA 폐색 1 시간 후 생산되는 사이토카인 양에 미치는 효과 = 27
2) 재관류 1 시간 후 생산되는 사이토카인 양에 미치는 효과 = 29
Ⅳ. 考察 = 31
Ⅴ. 結論 = 38
參考文獻 = 40