舒芬太尼对阿尔茨海默症大鼠认知功能和氧化应激及炎症反应的影响

Effects of sufentanil on cognitive function,oxidative stress and inflammatory response in Alzheimer's disease model rats

目的舒芬太尼对神经元细胞有保护作用,但在阿尔茨海默症(AD)体内实验研究相对较少。文中旨在探讨舒芬太尼对AD模型大鼠认知功能、氧化应激和炎症反应的影响。方法将Aβ1-42用无菌生理蒸馏水稀释制作AD模型。50只SD级雄性大鼠分为5组,分别为对照组、AD组、舒芬太尼低剂量组(1μg/kg)、舒芬太尼高剂量组(10μg/kg)和石杉碱甲组(30μg/kg),每组10只采用Morris水迷宫实验检测大鼠学习、认知功能;Western blot检测大鼠海马区突触囊泡膜蛋白(SYP)和突触后致密物-95(PSD95)的蛋白表达;酶联免疫法(ELISA)检测各大鼠的胆碱乙酰基转移酶(ChAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、TNF-α和IL-1β。结果 AD组的逃避潜伏期、原平台象限停留的时间、跨平台次数较对照组、舒芬太尼低剂量组、舒芬太尼高剂量组、石杉碱甲组明显延长(P<0.05)。AD组SYP、PSD95蛋白表达较对照组、舒芬太尼低、高剂量组、石杉碱甲组明显降低(P<0.05)。AD组的ChAT、AChE活性[(6.7±0.8)、(45.6±4.9)]较对照组[(16.8±1.9)、(98.3±10.1)]、舒芬太尼低剂量组[(9.3±0.7)、(61.2±5.3)]、舒芬太尼高剂量组[(14.2±1.1)、(86.7±7.3)]和石杉碱甲组[(13.9±1.3)、(89.7±8.5)]明显降低(P<0.05)。AD组的SOD活性、CAT活性较对照组、舒芬太尼低、高剂量组和石杉碱甲组明显降低(P<0.05),MDA含量、TNF-α、IL-1β表达明显增加(P<0.05)。结论舒芬太尼对Aβ1-42诱导的AD模型大鼠认知功能损伤具有保护作用,可能与调节胆碱系统、调节突触相关蛋白、抗氧化和抗炎有关。

Objective Sufentanil has a protective effect on neurons, but there are relatively few experimental studies in vivo on Alzheimer’s disease(AD). This study aims to investigate the effects of Sufentanil on cognitive function, oxidative stress and inflammatory response in AD model rats. Methods The Aβ1-42 coefficient was diluted with sterile physiological distilled water to make AD model. Fifty SD male rats were divided into 5 groups: control group, AD group, Sufentanil low-dose group(1 μg/kg), Sufentanil high-dose group(10 μg/kg) and Huperzine A(30 μg/kg), 10 rats in each group were tested for learning and cognitive function by Morris water maze test. The expression of synaptic vesicle membrane protein(SYP) and postsynaptic denser(PSD95) in hippocampal region of rats were detected by Western blot. The levels of choline acetyltransferase(ChAT), acetylcholinesterase(AChE), superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), TNF-α And IL-1β were detected by Enzyme-linked immunoassay(ELISA). Results Compared with the control group, Sufentanil low-dose group, Sufentanil high-dose group and Huperzine A group, the latency of escape, the time of stay in original platform quadrant and the number of cross-platform in AD group were significantly longer(P<0.05). The protein expressions of SYP and PSD95 in AD group were significantly lower than those in control group, Sufentanil low-dose group, high-dose group and Huperzine A group(P<0.05). The ChAT and AChE activities in AD group [(6.7±0.8),(45.6±4.9)] were higher than those in control group [(16.8±1.9),(98.3±10.1)], Sufentanil low-dose group [(9.3±0.7),(61.2±5.3)], Sufentanil high-dose group [(14.2±1.1),(86.7±7.3)] and Huperzine A group [(13.9±1.3),(89.7±8.5)] significantly decreased(P<0.05). Compared with the control group, Sufentanil low-dose and high-dose groups and Huperzine A group, the activities of SOD and CAT in AD group were significantly decreased(P<0.05), and the expression the content of MDA, TNF-α, IL 1β was significantly increased(P<0.05). Conclusion Sufentanil can protect the cognitive function injury of AD rats induced by Aβ1-42, which may be associated with regulation of choline system, synaptic associated proteins, antioxidant and anti-inflammatory factors.