摘要
目的通过动物实验,观察复方氯胺酮口服液(Compound ketamine oral solution,CKOS)对大鼠胃NMDAR1、GABAA受体的影响,探讨其对胃肠动力的调节机制,并进一步评价其临床应用的安全性。方法选择雄性、健康SD大鼠50只,随机分10个时间点,每个时间点5只大鼠。0点为对照组,经灌胃器注2μL/g生理盐水,其他各点将CKOS[含氯胺酮(Ketamine,KET)100mg/kg,咪达唑仑(Midazulum,MID)10mg/kg]灌入胃内。采用免疫组化和原位杂交的方法,观察服药后10个点大鼠胃NMDAR1、GABAA受体的变化。显微(荧光)图像分析系统对切片进行采集分析。结果用CKOS后10min,NMDAR1表达开始减少,15～120min NMDAR1明显减少,240min时开始恢复,但仍然低于对照组。360min时仍未恢复到正常水平。用CKOS后30min,GABAA R表达开始增加,60～90min GABAA R表达明显增加,240min时开始恢复,360min时恢复到正常水平。结论CKOS抑制胃排空可能与其能够抑制胃NMDAR1受体的表达、增强GABAA受体的表达有关。
Objective To observe the effects of compound ketamine oral solution（CKOS）on rats gastric NMDAR1 and GABAA receptors in order to find out the effects of CKOS on gastrointestinal motility,and evaluate the security of CKOS.Methods Fifty male healthy Sprague-Dawley rats were randomly divided into 10 time points.Each time point had 5 rats.Rats in 0 min time point were irrigated with 0.9%NS 2 μL/g for contrast.Others were irrigated with CKOS 2 μL/g（KET 100 mg/kg,MID 10 mg/kg）.After drug administration respectively at the time of 0,5,10,15,30,60,90,120,240,360 min,catheter was inserted from right heart to irrigate 0.9% cold NS,the colour of liver changed from red to white（150 mL）,extra fluid were removed from venecava.Then after all body organs were fixed with 4% polymaldehyde,stomach were taken out and put into 4 ℃ refrigerator,the changes of NMDAR1、GABAAR in rats stomach were observed by immune histochemistry staining and in situ hybridization.Results The NMDAR1 expression began to decrease at 10 min after taking CKOS,and decreased significantly between 15~120 min,recovered at 240 min,but was still lower than control group.At 360 min,it was still unrecovered.The GABAAR expression began to increase at 30 min after taking CKOS,increased significantly at 60～90 min. Recovery began at 240 min,and it recovered to normal at 360 min.Conclusion CKOS can inhibit the expression of NMDAR1 and increase the expression of GABAAR in rats′ stomach,which may be one of the reasons for CKOS slowering gastric fluid emptying in rats.
出处
《实用药物与临床》
CAS
2010年第2期83-86,共4页
Practical Pharmacy and Clinical Remedies
基金
辽宁省自然基金(20062085)
辽宁省教委基金(05L461)
