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주정투여 및 금단이 백서 뇌 및 간 adenosine triphosphatase 활성에 미치는 영향

주정투여 및 금단이 백서 뇌 및 간 adenosine triphosphatase 활성에 미치는 영향
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대학원 의학과
이화여자대학교 대학원
The major action sites of alcohol are brain and liver, though it is not still clarified how the changes affect on the formation of tolerance and dependence. Recently proposed, alcohol primarily acts on the synaptic membranes, causing widespread changes in neurotransmission via effects on the numerous biochemical processes. That is to say, alcohol inhibits action potentials and active transports of cations, in which ATPase plays an important role as a carrier. The activities of membranebound enzymes such as Mg^++ ATPase and (Na^+ - K^+ )ATPase are influenced by alcohol. The author investigates on the changes of ATPase activities when ethanol is administered acutely, chronically up to 3 weeks, and withdrawan 6 hours after the last dose of ethanol up to 72 hours, to account with the effect of ethanol on sodium pump and cation transport. The results obtained are as follows: 1. Upon acute ethanol(30% w/v) administration, brain homogenates showed more significantly increased Mg^++ ATPase activities than control group only in small amount of ethanol treated groups after 1 hour and 2 hours.(Na^+ - K^+ )ATPase activities were in decreasing trend rather than the control group, even though amount of ethanol was increased and reaction time was prolonged, but there was no statistical significance. After 1 hour, only (Na^+ - K^+ ) ATPase activities were gradually decreased according to the increased of ethanol amount in liver homogenates, which were significantly decreased rather than control groups after 2 hours. 2. Upon chronic ethanol(14% w/v) administration, brain homogenates showed significantly increased Mg^++ ATPase activities in 2 weeks and 3 weeks group as increased of (Na^+ - K^+ )ATPase activities in 3 weeks group. In liver homogenates, Mg^++ (Na^+ - K^+ )ATPase and Mg^++ ATPase activities were significantly increased than controls according to lapse of time, but (Na^+ - K^+ )ATPase activities were significantly decreased. 3. Upon ethanol withdrawal after chronic ethanol(14% w/v) administration for 3 weeks, brain homogenates showed that Ma^++ (Na^+ - K^+ )ATPase activities began to decrease significantly than chronic ethanol treated groups after 12 hours of withdrawal, which ws approximated to the control level. (Na^+ - K^+ )ATPase activities began to increase after 6 hours, reaching to the maximal level after 24 hours, which was followed by slight decrease after 48 hours and reincrease after 72 hours, being approximated to normal control group. In liver homogenates, Mg^++ (Na^+ - K^+ )ATPase activities showed no significant changes than 3 weeks ethanol treated groups with lapse of withdrawal time, but began to decrease after 6 hours, being significantly increased after 24 hours than normal controls. Mg^++ ATPase activities began to decrease gradually after 6 hours according to lapse of time, but it was significantly increased than normla controls. (Na^+ - K^+ )ATPase activities were gradually increased according to lapse of withdrawal time. To be suppressed when ethanol is administered acutely or chronically, because (Na^+ - K^+ )ATPase activities in liver homogenates are decreased and liver weight is increased, although acute ethanol administration cannot affect on the (Na^+ - K^+ ) ATPase activities. In brain, (Na^+ - K^+ ) ATPase activities are decreased according to prolongation of duration on ethanol administration, and brain weight become slightly increased in 1-2 weeks with no changes in 3 weeks group, which suggest that sodium pump may be decreased and cation transports are inhibited. Upon lapse of ethanol withdrawal time, brain and liver (Na^+ - K^+ )ATPase activities are increased to return to the normal control level, which suggest that a certain compensatory mechanisms are exerted. ; 주정의 작용부위는 주로 중추신경계와 간장이며, 뇌와 간장의 병적변화가 주정의 어떤 영향에 의하는 것인지는 아직도 잘 알려져 있지 아니하나, 세포적·대사적·행동적 측면에서 연구되고 있다. 주정은 일차적으로 연접부 막에서의 여러 생화학적 과정에 변화를 일으킬 수 있다. 주정은 세포막의 활동전위와 Na-K pump에 필요한 에너지의 유리를 억제하며, 따라서 주정은 막 결합효소인 (Na^+ - K^+ ) ATPase 및 Mg^++ ATPase의 활성에 영향을 미친다. 이상을 기초로 하여 저자는 주정의 급성투여시, 만성투여시 및 금단시의 막에 결합된 효소활성을 측정하여 다음과 같은 결과를 얻었다. 1. 30%(W/V) ethanol 급성투여시, 뇌 homogenates에서는 1시간 및 2시간후 주정을 소량 투여한 군에서만 대조군에 비하여 Mg^++ ATPase의 활성도가 유의하게 증가되었으며, (Na^+ - K^+ )ATPase 활성도는 주정투여를 증가시키고 작용시간을 경과시켜도 대조군에 비해서는 감소되는 경향이나 통계적으로 유의한 변화는 아니다. 간 homogenates에서는 1시간 경과후에 (Na^+ - K^+ )ATPase 활성도만이 주정용량 증가에 따라 점차 감소되었고, 2시간 경과후에는 대조군에 비하여 유의하게 감소되었다. 2. 14%(W/V) ethanol 만성투여시, 뇌 homogenates에서는 2주 및 3주군에서 Mg^++ ATPase 활성도가 유의하게 증가되었고, (Na^+ - K^+ )ATPase는 3주군에서만 유의하게 감소되었다. 간 homogenates에서는 시간이 경과되는데 따라 Mg^++ (Na^+ - K^+ )ATPase 및 Mg^++ ATPase 활성도는 대조군에 비하여 유의하게 증가되었고, (Na^+ - K^+ )ATPase 활성도는 유의하게 감소되었다. 3. 14%(W/V) ethanol 3주 투여후 금단시, 뇌 homogenates에서는 12시간 후부터 Mg^++ (Na^+ - K^+ )ATPase 및 Mg^++ ATPase 활성도는 만성투여군에 비해 유의하게 감소되나 정상대조군의 값과 유사하다. (Na^+ - K^+ )ATPase 활성도는 6시간후부터 상승되어 24시간에 최고값에 달하고, 48시간 후에 일시 감소되다가 72시간후 다시 증가되어 정상 대조군 값에 가까워졌다. 간 homogenates에서는 Mg^++ (Na^+ - K^+ )ATPase 활성도는 금단시간이 경과해도 32주동안 ethanol 투여군에 비해 변화가 없으나 정상 대조군에 비해서는 유의하게 증가되었고, Mg^++ ATPase 활성도는 6시간 후부터 시간이 경과함에 따라 계속 유의하게 감소하였으나 정상 대조군에 비해서는 유의하게 증가되었다.(Na^+ - K^+ )ATPase 활성도는 금단시간이 경과함에 따라 계속 증가되었다. 이상의 실험결과로 보아 뇌에서 주정의 급성투여는 (Na^+ - K^+ )ATPase에 영향을 미치지 못한다. 만성투여로 투여기간이 연장됨에 따라 (Na^+ - K^+ )ATPase 활성도가 감소되고, 1주 및 2주군에서는 뇌의 무게가 증가하는 것으로 추정되며, 3주군에서는 뇌무게의 변화가 없었다. 급성으로나 만성으로 주정을 투여하였을 때 간(Na^+ - K^+ ) ATPase 활성도는 감소되고 간의 무게가 증가되는 것으로 보아 Na-pump가 억제되는 것으로 추정된다. 금단시간이 경과함에 따라 뇌 및 간의 (Na^+ - K^+ )ATPase 활성이 증가하여 정상 대조군 값으로 되돌아오는 것으로 보아 보상이 되는 것으로 추정된다.
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