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선천성 고혈압쥐의 고혈압발생과 뇌내 Prostaglandin - E₂와의 상관관계

선천성 고혈압쥐의 고혈압발생과 뇌내 Prostaglandin - E₂와의 상관관계
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대학원 약학과
이화여자대학교 대학원
The purpose of this study is to investigate the relationship between the development of hypertension and brain PGE_2 level in the spontaneously hypertensive rats (SHR) and also, to determine whether this relationship is orginated from the genetic factor. To achieve this, we have measured the levels of endogenous brain PGE_2 and systolic blood pressure (blood pressure) with age both in the SHR and normotensive rats (NTR). Also, we have compared the blood pressure and PGE_2 level in the brain with stress and treatment of antihypertensive drugs between SHR and DOCA-salt treated rats. The levels of endogenous brain PGE_2 have been determined by employing the radioimmunoassay method, and blood pressures were measured indirectly by employing the tail-cuff plethysmograph. As the age was increased, differences between the SHR and NTR were found in the age of the decreasing brain PGE_2 level and the correlation coefficient between blood pressure and brain PGE_2 level. The SHR showed a stronger negative correlation in the relationship between blood pressure and brain PGE_2 level than the NTR. Under a 5-day stress condition, the age-matched NTR showed a little variation in blood pressure but significant increase in the brain PGE_2 level. In contrast, the SHR showed a significant variation in blood pressure but nearly constant brain PGE_2 level. When the stress was subjected to the clonidinetreated SHR and DOCA-salt treated rats, hypertension was significantly reduced in both rats and the SHR showed a bigger change in the brain PGE_2 level than the DOCA-salt treated rats. While, in the case of Aloe ext. treatment, hypertension in the SHR was significantly reduced but that in the DOCA-salt treated rats was not reduced. In this case, a contrasting behavior was observed in the sense that the brain PGE_2 level in the SHR was decreased but that in the DOCA-salt treated rats was increased. Thus, the responses of blood pressure and brain PGE_2 level to the hypertension inducing factors were quite different between the SHR and normal rats. While the underlying mechanisms for these differential responses are not understood yet, the obtained results indicate that these differences may have their origins at the genetic level. ; 선천성고혈압쥐는 사람의 본태성고혈압과 가장 유사한 실험모형으로써 본태성고혈압의 원인 규명을 위해 많이 이용되어 오고 있다. 본 실험에서는 동물의 성장과정에 따른 혈압변동과 이때 뇌중 PGE_2 함량을 정상혈압쥐와 선천성 및 후천성고혈압쥐에서 비교 관찰하고 자극이나 항 고혈압약 투여로 인한 혈압과 뇌중 PGE_2가 고혈압에 미치는 작용기전에 유전적요인의 관련여부를 규명해 보고자 하였다. 1. 연령증가에 따라 뇌중 PGE_2함량이 선천성고혈압쥐에서 유의성 있게 감소하였으며 (P<0.01) 정상혈압쥐에 비해 혈압과 뇌중 PGE_2함량사이의 상관계수가 선천성고혈압쥐에서 더 큰 것으로 나타났다(r=-0.981). 2. Stress 부하로 인한 혈압변동은 정상혈압쥐보다 선천성고혈압쥐에서 현저하였으며(P<0.01) 뇌중 PGE_2함량변화는 정상혈압쥐에서 43.5%의 유의성있는 증가를 하였다. 3. Clonidine(100μg/kg/day, i.p.) 투여는 stress 부하한 선천성고혈압쥐 및 후천성고혈압쥐의 고혈압상태를 억제하였으며 뇌중 PGE_2 함량은 각각 약물투여하지 않은 대조군에 비해 증가하였으나 두 동물군사이에는 양적차이가 있었다. 4. 알로에추출물 (480mg/kg/day, p.o.) 투여는 stress 부하한 선천성고혈압쥐의 고혈압진전 상태를 억제하였고 stress 부하한 후천성고혈압쥐의 고혈압발현에는 큰 영향을 미치지 못하였다. 뇌중 PGE_2함량은 선천성고혈압쥐에서는 대조군에 비해 30.2% 감소되었으나 후천성고혈압쥐에서는 26.2%의 증가를 나타내는 서로 상반된 현상이었다. 이상 실험결과 선천성고혈압쥐에서 뇌중 PGE_2량이 정상혈압쥐보다 결핍된 것은 고혈압을 발현하는 유전적 특징일 수 있으며 특히 선천성고혈압쥐와 후천성고혈압쥐 사이의 뇌중 PGE_2함량의 증감이 서로 상반된 것은 선천적으로 가지는 유전적요인이 관련된 결과라고 생각된다.
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