三种对挥发性麻醉剂敏感度不同的黑腹果蝇品系的培育

Liu Jin, Hu Zhao-yang, Ye Qi-quan, Dai Shuo-hua

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

Chin Med J (Engl). 2009 Mar 5;122(5):561-5.

BACKGROUND

The mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved.

METHODS

Median effective doses (ED(50)) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6 - 10 were cultured for breeding sensitive offspring (S(1)). So did median ones of percentile 48 - 52 for breeding median offspring (M(1)), resistant ones of percentile 91 - 95 for breeding resistant offspring (R(1)). Process was repeated through 31 generations, in the 37th generation, S(37), M(37) and R(37) were used to determine ED(50) for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane, chloroform and trichloroethylene, then ED(50) values were correlated with minimum alveolar concentration (MAC) values in human.

RESULTS

From a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED(50) values in three strains correlated directly with MAC values in human.

CONCLUSIONS

Three Drosophila melanogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED(50) are directly correlated with MAC in human for eight volatile anesthetics.

背景

几个世纪以来，挥发性麻醉剂的作用机制一直不明，部分原因是研究模型不足或无效。我们设计了本研究，以培育出三种源自野生型黑腹果蝇的品系，它们对挥发性麻醉剂具有不同的敏感性，这最终可能有助于对相关机制进行分子和遗传学研究。

方法

测定七日龄未交配的野生型黑腹果蝇雌、雄个体对七氟醚的半数有效剂量（ED(50)）。选择百分位数为6 - 10的敏感雌、雄果蝇进行培育，以产生敏感后代（S(1)）。对百分位数为48 - 52的中等敏感果蝇和百分位数为91 - 95的抗性果蝇也进行同样操作，分别培育中等敏感后代（M(1)）和抗性后代（R(1)）。此过程重复31代，在第37代时，使用S(37)、M(37)和R(37)来测定它们对恩氟醚、异氟醚、七氟醚、地氟醚、氟烷、甲氧氟烷、氯仿和三氯乙烯的ED(50)，然后将ED(50)值与人类的最低肺泡浓度（MAC）值进行相关性分析。

结果

我们从野生型黑腹果蝇培育出了对七氟醚需求高、中等和低的三种品系。三种品系对七氟醚的需求比例，雌性为1.20:1.00:0.53，雄性为1.22:1.00:0.72。对七氟醚敏感、中等敏感和抗性的品系对其他挥发性麻醉剂也分别表现出敏感（原文sensitive应为sensitive）、中等敏感和抗性。对于八种麻醉剂，三种品系的ED(50)值与人类的MAC值直接相关。