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探讨胆碱(Cho)与对乙酰氨基酚(Ace)的协同镇痛作用及其机制。本研究采用腹腔注射0.6%醋酸溶液建立小鼠醋酸扭体疼痛模型。将KM小鼠随机分为对照组(n=10)、单用Cho组(n=50)、单用Ace组(n=50)和合用组(n=40),造模后计数20 min内扭体次数。采用Origin Pro8.5软件分析求得各药物的ED50。采用等辐射分析法分析Cho和Ace的相互作用。为进一步研究Cho和Ace协同作用的机制,将40只KM小鼠随机分为生理盐水对照组(control组)、Cho组、Ace组和Cho+Ace组,每组10只。造模后,小鼠眼球取血,使用ELISA试剂盒分别测定小鼠血清中TNF-α、IL-6、PGE2、NF-κB的含量。经计算可得,单用Cho组和单用Ace组的ED50分别为19.47和20.56 mg·kg~(-1),合用组ED50为Cho 2.94 mg·kg~(-1)+Ace 3.15 mg·kg~(-1)。等辐射分析法证实Cho与Ace合用时具有协同镇痛作用。ELISA结果发现Cho组和Ace组血清中TNF-α、IL-6、PGE2和NF-κB含量较control组降低(P<0.05),而与Cho组和Ace组相比,Cho+Ace组TNF-α、IL-6、PGE2和NF-κB含量进一步降低,且差异具有统计学意义(P<0.05)。本研究证实Cho与Ace具有协同镇痛作用,其机制可能与抑制NF-κB信号通路的激活有关。
To investigate the synergistic analgesic effect of cholinergic and acetaminophen (Ace) and its mechanism. In this study, mouse acetic acid writhing pain model was established by intraperitoneal injection of 0.6% acetic acid solution. KM mice were randomly divided into control group (n = 10), Cho group alone (n = 50), Ace group (n = 50) alone and combined group Twisting the number of times. Origin Pro8.5 software was used to analyze the ED50 of each drug. Radiometric analysis was used to analyze the interaction between Cho and Ace. To further investigate the mechanism of synergy between Cho and Ace, 40 KM mice were randomly divided into saline control group, Cho group, Ace group and Cho + Ace group, with 10 mice in each group. After model establishment, mice were bled by eyeball. The contents of TNF-α, IL-6, PGE2 and NF-κB in serum were determined by ELISA kit. The calculated ED50 of Cho group and Ace group alone were 19.47 and 20.56 mg · kg -1, respectively. The ED50 of combined group was Cho 2.94 mg · kg -1 and Ace 3.15 mg · kg -1 ~ (-1). Radiometric analysis confirmed that Cho and Ace had synergistic analgesic effects. The levels of TNF-α, IL-6, PGE2 and NF-κB in Cho group and Ace group were significantly lower than those in control group (P <0.05) by ELISA. Compared with Cho group and Ace group, α, IL-6, PGE2 and NF-κB levels were further decreased, with statistical significance (P <0.05). This study confirmed that Cho and Ace have a synergistic analgesic effect, the mechanism may be related to the inhibition of NF-κB signaling pathway activation.