GLP是英文Good Laboratory Practice for Nonclinical Safety Studies的缩写。中文译为“药物非临床安全性试验质量管理规范”。 60年代以前,药政部门和毒理学界对药品安全性关心的重点是如何制订一套完善的毒性试验技术要求。对毒性试验的动物种属、给药途径、剂量选择、试验期限以及观测的指标等,提出了一套“量的规范”。由于“药害事件”的不断发生,70年代以后,除了“量的规范”不断完善和日趋严格之外,又提出了毒性试验过程的质量控制问题,即“质的规范”,使药品的安全性试验步入了一个新的阶段。 1974年美国参议院出于对药品安全性的关心。
Aim Intracellular calcium ([Ca^(2+) ]_i) is mainly regulated by mitochondriaand endo-plasmic reticula. This study was carried out to ascertain whether the elementary mechanismof the effects of etimicin (EM) and gentamicin (GM) on [Ca^(2+) ]_i is related to their effects onmitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake. Methods The effects of GMand EM on [Ca^(2+) ]_i in LLC-PK1 were determined with a fluorescent probe of Fura-2/AM. The effectsof EM and GM on mitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake weredetermined by isotope indicator (^(45)Ca^(2+) ) . Results EM and GM at the concentration of 1mmol·L^(-1) had no significant effect on [Ca^(2+) ]_i(P. > 0.05) and at 10 mmol·L^(-1)significantly caused [Ca^(2+) ]_i to increase (P < 0.01). EM and GM at 1 mmol·L^(-1) causedmitochondrion Ca^(2+)-uptake to ascend dramatically (P < 0.05) and at 10 mmol·L^(-1) causedmitochondrion Ca^(2+) -uptake to descend significantly. EM and GM at more than 0.34 mrnol·L^(-1)significantly inhibited endoplasmic reticulum Ca^(2+) -uptake (P < 0.05 or 0.01). Conclusion Novariation of [Ca^(2+) ]_i caused by EM and GM at lower concentrations might relate to theequilibrium of their promotion of mitochondrion Ca^(2+) -uptake with their inhibition of endoplasmicreticulum Ca^(2+) -uptake. The elevation of [Ca^(2+) ]_i caused by EM and GM at higherconcentrations might correlate with their inhibition of mitochondrion Ca^(2+) -uptake andendoplasmic reticulum Ca^(2+) -uptake.
