糖尿病孕鼠七氟醚麻醉对子代大鼠认知功能的影响

Effect of sevoflurane anesthesia in diabetic pregnant rats on cognitive function of offspring rats

目的探讨糖尿病孕鼠七氟醚麻醉对子代大鼠认知功能的影响。方法SD大鼠雌鼠40只，雄鼠5只，体重200～250 g，孕7 d时随机取20只孕鼠，采用腹腔注射链脲佐菌素45 mg/kg的方法制备糖尿病模型。取未制备模型的孕20 d大鼠20只，采用随机数字表法分为2组（n＝10）：七氟醚组（S组）和对照组（C组）；取糖尿病造模成功的孕20 d大鼠20只，采用随机数字表法分为2组（n＝10）：七氟醚组（DS组）和对照组（DC组）。DS组和S组孕鼠放入自制麻醉箱吸入2%七氟醚2 h。于子代大鼠出生6周时进行Morris水迷宫实验，处死后取海马和皮质组织，采用免疫组化法测定磷酸化cAMP反应元件结合蛋白（p-ERCB）的表达。结果与C组比较，S组和DC组子代大鼠逃避潜伏期延长，穿越平台次数减少（P〈0.05）；与DC组比较，DS组子代大鼠穿越平台次数减少，逃避潜伏期延长（P〈0.01）；与S组比较，DS组逃避潜伏期延长，穿越平台次数减少（P〈0.05），海马区及皮质区p-CREB染色较浅，阳性细胞数减少。结论七氟醚麻醉可加重糖尿病孕鼠子代的认知功能障碍，机制与抑制CREB磷酸化有关。

ObjectiveTo investigate the effects of sevoflurane anesthesia in diabetic pregnant rats on the cognitive function of the offspring rats.MethodsForty female Sprague-Dawley rats and 5 male rats, weighing 200-250 g, were used in the study.Twenty pregnant rats at 7 weeks of gestation were randomly selected, and diabetes mellitus was induced by intraperitoneal streptozotocin 45 mg/kg and confirmed by blood glucose level 〉10.4 mmol/L.Twenty pregnant rats at 20 days of gestation, in which diabetes mellitus was not induced, were selected and divided into 2 groups（n=10 each）using a random number table： sevoflurane group（group S）and control group（group C）. Twenty pregnant rats at 20 days of gestation with diabetes mellitus were selected and divided into 2 groups（n=10 each） using a random number table： sevoflurane group（group DS）and control group（group DC）. In DS and S groups, the pregnant rats were placed in a self-made anesthetic box and inhaled 2% sevoflurane for 2 h. At 6 weeks after birth, the offspring rats were selected, and Morris water maze test was performed.The rats were sacrificed, brains were removed, and the hippocampi and cortex were removed for determination of phosphorylated cyclic adenosine monophosphate response element-binding protein（p-CREB）expression using immuno-histochemistry.ResultsCompared with group C, the escape latency was significantly prolonged, and the frequency of crossing the original platform was significantly decreased in S and DC groups（P〈0.05）. Compared with group DC, the escape latency was significantly prolonged, and the frequency of crossing the original platform was significantly decreased in group DS（P〈0.01）. Compared with group S, the escape latency was significantly prolonged, the frequency of crossing the original platform was significantly decreased（P〈0.05）, and lighter staining for p-CREB was found, and the number of p-CREB positive cells was decreased in the hippocampus and cortex in group DS.ConclusionSevoflurane anesthesia-induced cognitive dysfunction is aggravated in the offspring rats of diabetic pregnant rats, and the mechanism is related to inhibition of CREB phosphorylation.