吗啡与舒芬太尼交替用药对大鼠中脑导水管周围灰质μ受体表达的影响  

Effect of opioid switch from morphine to sufentanil on expression of μ-opioid receptors in midbrain periaqueductal gray of rats

作　　者：刘晓艳[1] 董彦鹏[1] 孙莉[1] 

机构地区：[1]中国医学科学院肿瘤医院麻醉科,北京市100021

出　　处：《中华麻醉学杂志》2016年第6期697-700,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价吗啡与舒芬太尼交替用药对大鼠中脑导水管周围灰质（PAG）μ受体表达的影响。方法40只健康雄性Wistar大鼠，体重250～290g，8周龄，采用随机数字表法，将其分为5组（n=8）：正常对照组（C组）、7d舒芬太尼组（S组）、7d吗啡组（M组）、14d吗啡组（MM组）和14d吗啡与舒芬太尼交替组（MS组）。C组、S组和M组分别颈部皮下注射生理盐水2ml／kg、舒芬太尼0．01mg／kg或吗啡10mg／kg，连续7d；MM组颈部皮下注射吗啡10mg／kg，连续14d，MS组第1—7天颈部皮下注射吗啡10mg／kg，第8-14天颈部皮下注射舒芬太尼0．01mg／kg；上述药物2次／d。分别于每天首次给药后15min或30min时测定热甩尾潜伏期（TFL），最后一次给药后处死大鼠，分离PAG，采用RT—PCR法和Western blot法测定μ受体及其mRNA表达。结果与C组比较，M组、MM组和MS组给药第1—6天TFL延长，S组给药第1—7天TFL延长，M组、MM组和MS组PAG区μ受体及其mRNA表达下调（P〈0．05）；与MM组比较，MS组给药第8—14天TFL延长，PAG区μ受体及其mRNA表达上调（P〈0．05）。结论吗啡与舒芬太尼交替用药减轻大鼠吗啡耐受的机制与增强PAG区μ受体活性有关。Objective To evaluate the effect of the opioid switch from morphine to sufentanil on the expression of μ-opioid receptors in the midbrain periaqueduetal gray （PAG） of rats. Methods Forty healthy male Wistar rats, aged 8 weeks, weighing 250-290 g, were randomly assigned into 5 groups （n= 8 each） using a random number table： control group （group C） , 7 day sufentanil group （ group S） , 7 day morphine group （group M） , 14 day morphine group （group MM） , and 14 day alternate administration of morphine and sufentanil group （group MS）. Normal saline 2 ml/kg, sufentanil 0. 01 mg/kg and morphine 10 mg/kg were injected subcutaneously in the cervical region twice a day for 7 consecutive days in C, S and M groups, respectively. In group MM, morphine 10 mg/kg was injected subcutaneously in the cervical region twice a day for 14 consecutive days. In group MS, morphine 10 mg/kg was injected subcutaneously in the cervical region twice a day for 7 consecutive days （ 1st-7th days） , and sufentanil 0.01 mg/kg was then injected subcutaneously in the cervical region twice a day for 7 consecutive days （8th-14th days）. The tail flick latency （TFL） to a thermal noeiceptive stimulus was measured at 15 and 30 rain after the initial administration every day. After the last administration, the rats were sacrificed, and the midbrain PAG was isolated for determination of the expression of the μ-opioid receptor and μ-opioid receptor mRNA using Western blot and real-time reverse transcriptase polymerase chain reaction, respectively. Results Compared with group C, the TFL was significantly prolonged on 1st-6th days after the beginning of administration in M, MM and MS groups, the TFL was significantly prolonged on lst-7th days after the beginning of administration in group S, and the expression of the μ-opioid receptor and μ-opioid receptor mRNA in the midbrain PAG was significantly down-regulated in M, MM and MS groups （P〈0.05）. Compared with group MM, the TFL was significantly prolonged on

关 键 词：吗啡 舒芬太尼 受体 阿片样 μ 脑导水管 水管周灰质 

分 类 号：R965[医药卫生—药理学]