仙茅苷注射液对老年大鼠丙泊酚麻醉后认知功能的影响及机制

Effect and Mechanism of Curculigoside Injection on Cognitive Function of Aged Rats After Propofol Anesthesia

目的:探讨仙茅苷注射液对老年大鼠丙泊酚麻醉后认知功能的影响及作用机制。方法:将60只清洁级老年大鼠抽取50只建立丙泊酚麻醉模型,将成模大鼠采用随机数字表分为模型组、三七总皂苷(10 mg/kg)组及仙茅苷低(24 mg/mL)、中(48 mg/mL)、高(72 mg/mL)剂量组。剩余10只大鼠作为正常对照组。各给药组腹腔注射给药,模型组腹腔注射相应体积生理盐水。给药次日采用Morris水迷宫实验评价大鼠认知功能;酶联免疫吸附试验(ELISA)检测海马组织IL-6、MDA水平;苏木素-伊红(HE)染色观察大鼠海马组织病理学;原位末端标记法(TUNEL)检测大鼠海马组织神经元凋亡;实时-逆转录(RT-qPCR)检测大鼠海马组织Nrf2、HO-1、mBDNF、Akt、CREB mRNA表达;蛋白质免疫印迹法(Western Blot)检测大鼠海马组织Nrf2、HO-1、mBDNF、Akt、CREB、p-Akt、p-CREB蛋白表达。结果:模型组逃避潜伏期显著长于正常对照组,穿越原平台的次数显著少于正常对照组,空间探索时间显著短于正常对照组,海马组织IL-6、MDA含量及海马神经元凋亡率和海马组织Nrf2、HO-1 mRNA与蛋白表达均显著高于正常对照组,海马组织mBDNF、Akt、CREB mRNA与蛋白表达及p-Akt、p-CREB蛋白表达显著低于正常对照组;三七总皂苷组和仙茅苷各剂量组上述指标均较模型组显著改善;模型组海马组织呈明显病理改变,各给药组海马病变明显减轻。结论:仙茅苷可改善老年大鼠丙泊酚麻醉后的认知功能,其机制与抑制Nrf2/HO-1通路、激活mBDNF/Akt/CREB通路有关。

Objective:To investigate the effect and mechanism of curculigoside injection on cognitive function of aged rats after propofol anesthesia.Methods:50 of 60 SPF old rats were selected to establish propofol anesthesia model,and the model rats were randomly divided into model group,Panax notoginseng total saponin(10 mg/kg)group,curculigoside low(24 mg/mL),medium(48 mg/mL)and high(72 mg/mL)dose groups.The other 10 rats were recorded as normal group.The rats of each drug group were intraperitoneally injected with corresponding drugs,the model group rats were given the same amount of normal saline.Morris water maze test was used to evaluate the cognitive function on the next day.The IL-6 and MDA levels in hippocampus were detected by ELISA.Hematoxylin-Eosin(HE)staining was used to observe the pathological changes of rat hippocampus.TUNEL was used to detect the apoptosis of rat hippocampal neurons.The expressions of Nrf2,HO-1,mBDNF,Akt and CREB mRNA in hippocampus were detected by RT-qPCR.The proteins expressions of Nrf2,HO-1,mBDNF,Akt,CREB,p-Akt and p-CREB were detected by Western Blot(WB).Results:The escape latency of model group was significantly longer than that of normal control group,the times of crossing the original platform was less than that of normal control group,and the space exploration time was significantly shorter than that of normal control group,the contents of IL-6 and MDA in hippocampus,apoptosis rate of hippocampal neurons,Nrf2 and HO-1 mRNA and proteins expressions were significantly higher than those in the normal control group,the mBDNF,Akt,CREB mRNA and protein expressions and the levels proteins expressions p-Akt and p-CREB in hippocampus were significantly lower than those in the normal control group.The above indexes in the Panax notoginseng total saponin group and curculigoside each group were significant improved compared with the model group.The pathological changes of hippocampus in the model group were obvious,the hippocampal lesions in all treatment groups were reduced.Conclusion:Curculigoside can improve the cognitive function in aged rats after propofol anesthesia,the mechanism may be related to inhibiting Nrf2/HO-1 pathway and activating mBDNF/Akt/CREB pathway.