암 생쥐에서 Testosterone으로 인한 유해감각예민도 둔화와 이에 대한 Naloxone의 차단효과
Testosterone-Induced Antinociception and It's Blockae by Naloxone in Female Mice
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Testosterone이 유해감각예민도에 미치는 영향과 아편성 기전의 관여 여부를 알아보고자 하였다. 성숙한 암 생쥐(Institute for Cancer Research) 37마리를 무작위로 naloxone군(N=18)과 대조군(N=19)으로 나누고, 실험 첫째 날과 셋째 날에 testosterone propionate 1 mg/kg와 함께 naloxone HCl 2mg/kg 혹은 생리 식염수 5ml/kg를 각각 복강내 주사하였다. 실험 첫째 날과 셋째 날에 약물 투여 전과 testosterone 투여 30 분 후(naloxone 투여 6분 후) 52℃ 물에 대한 tail flick latency(TFL, 초)로 유해감각 예민도를 측정하였다. 실험 둘째 날에는 두 군 모두 testosterone만 주사하였다. 그 결과는 다음과 같다. 1. Testosterone은 TFL로 측정한 유해감각예민도를 유의하게 둔화시켰다. 즉, 대조군의 실험 첫 날 testosterone과 생리식염수 투여 전후의 TFL은 각각 5.5±1.1초와 6.3±1.2초로서 유의한 변화가 있었다(t=4.07, p=0.001). 실험 셋째 날 약물 투여 전 TFL은 5.9±1.0초로서 실험 첫날보다 유의하게 둔해졌다(t=2.37, p=0.029). 2. Testosterone의 TFL 둔화효과는 naloxone으로 완전 차단되었다. 즉, naloxone군의 실험 첫날 testosterone과 naloxone 투여 전후의 TFL은 각각 5.6±0.8초와, 5.3±0.9초로서 변화가 없었다. 실험 셋째 날 약물 투여 전 TFL은 6.6±1.2초로서 실험 첫날보다 유의하게 둔해졌다(t=2.87, p=0.011). 약물 투여 후에는 5.3±1.3초로 유의하게 감소하였다(t=4.73, p=0.000). 이상의 결과에서, 암 생쥐에서 testosterone은 유해감각예민도를 둔화시키며, 그 기전에는 내인성 아편계가 관여한다고 제안한다.
Abstract
In order to examine the effect of testosterone on antinociception and the role of opioid system as an underlying mechanism, thirty-seven adult female mice(Institute of Cancer Research) were randomized to Naloxone(n=18) and Control group(n=19). Testosterone propionate(1mg/kg, ip) with naloxone HCL(2mg/kg, ip) or with normal saline(5ml/kg, ip) was administered on the first and the third experimental days. Nociceptive sensitivity was measured by Tail flick test(TFL, sec) before and after injection on the first and the third experimental days. The same dose of testosterone was injected on the second experimental day. The results were as follows; 1. TFL of control group was significantly increased by testosterone. TFL of control group measured on the first experimental day before and after injection were 5.5±1.1 sec(mean±sd) and 6.3±1.2 sec, respectively, and the change was significant(t=4.06, p=0.001). That measured on the third experimental day before injection was 5.9±1.0, showing a significant increase compared to that of the first experimental day(t=2.37, p=0.029). 2. Testosterone-induced antinociception was blocked by naloxone. In naloxone group, change in TFLs measured before(5.6±0.8) and after(5.3±0.9) injection was not significant on the first experimental day. On the third day, TFL measured before injection(6.6±1.2) was increased significantly than that of the first experimental day(t=2.87, p=0.011), but it decreased to baseline level after injection of naloxone(5.3±1.3; t=4.73, p=0.000). From these results, it is suggested that testosterone has antinociceptive effect, which is mediated by endogenous opioid system.