규칙적인 운동이 고혈압유발 흰쥐의 심근에서 Bcl-2발현 및 Apoptosis변화에 미치는 영향
The Effects of Regular Exercise on the Expression of Bcl-2 and Apoptosis in Myocardium of L-NAME Induced Hypertensive Rat.
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본 연구의 목적은 고혈압흰쥐에 있어서 규칙적인 운동이 항고혈압 및 심근에서의 세포자멸사를 예방하는 효과를 알아보는 것이다. 이에 본 실험에서는 흰쥐에 L-NAME를 투여하여 고혈압을 유발시킨 후 규칙적인 운동(수영)을 시행하여 수축기와 이완기혈압을 측정하였고, 심근에서의 세포자멸사현상을 TUNEL방법으로, 항세포자멸사인자인 Bcl-2발현현상을 면역조직화학염색법으로 분석하였다. 연구대상은 Sprague-Dawley계 숫컷 흰쥐 40마리를 대조군(n=10), L-NAME를 투여한 L-투여고혈압군(n=10), L-NAME를 투여와 운동을 시행한 L-투여고혈압운동군(n=10) 및 운동군(n=10)의 4군으로 분류하였고, 고혈압유도는 L-NAME(50mg/ kg)를 주당 5회, 총 8주간 투여하였다. 약물 투여 1시간 후 1일 1회 30분씩 운동을 시행하였고, 주 1회 혈압을 측정하였다. 수축기혈압과 이완기혈압은 L-NAME 투여 1주 후부터 증가하여 실험기간동안, 고혈압(p<.001)을 보였으나, L-투여고혈압운동군에서는 수영운동 4주후부터 실험종료때까지 지속적으로 혈압이 감소(p<.05)하였다. L-투여고혈압군의 심근세포에서는 자멸세포의 수가 증가되었으나, L-투여고혈압운동군에서는 세포자멸사가 억제된 소견을 보였다. 특히 세포자멸사를 억제시키는 Bcl-2의 발현은 L-투여고혈압운동군에서 L-투여고혈압군에 비해 뚜렷하게 증가되었으며, 대조군과 비슷한 발현양상을 보였다. 이상의 결과를 종합하면 8주간의 규칙적인운동은 고혈압 흰쥐의 혈압을 감소시켜 항고혈압효과를 나타내었고, Bcl-2의 발현으로 세포자멸사 증가가 억제함으로서 병적인 심장상태의 진행을 억제하는 효과가 있음을 알 수 있었다. 따라서 규칙적인 운동은 고혈압심장의 기능을 향상시켜 세포자멸사로부터 심장을 보호할 수 있는 것으로 생각된다.
Abstract
The present study was designed to examine the antihypertensive effects of regular exercise by suppressing apoptosis in myocardium of L-NAME induced hypertension rats. We measured systolic and diastolic blood pressure (BP), and performed Bcl-2 Immunohistochemistry and TUNEL for apoptosis in heart tissue. Sprague-Dawley (n=40) rats were divided into 4 groups as follows: (1) control group (n=10, Con), (2) hypertension group(n=10, L-Con) (3) hypertension+exercise group (n=10, L-Ex), (4) Exercise group (n=10, Ex). To induce hypertension we administrated L-NAME (50 mg/kg) for 5days per week during 8weeks. The regular exercise was performed in swim water bath for 30min after 1hr L-NAME administration. Both L-NAME treatment and swim were performed 5 days /week with duration of 30minutes for 8weeks. BP was measured once per week. Results showed that the BP was significantly increased (p<.001) from 1week after L-NAME treatment, but systolic BP of L-Ex(p<.001) and diastolic BP of Ex(p<.05) groups showed markedly decreased from 4weeks and 2weeks after exercise, respectively. Particulary, the Bcl-2 expression in L-Ex was markedly increased as compared with L-Con group, whereas L-Con group showed decreased Bcl-2 expression and increased apoptotic cell than other groups. These results suggest that regular exercise would induce anti-hypertensive effect by controling the BP and preventing the apoptosis through bcl-2 expression in myocardium of L-NAME treated rats. Thus, regular exercise may be helpful to improvement of hypertensive heart function.
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