大蒜素对模型小鼠的抗炎性痛作用及机制研究
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篇名: 大蒜素对模型小鼠的抗炎性痛作用及机制研究
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摘要: 目的:研究大蒜素对模型小鼠的抗炎性痛作用及机制。方法:50只BALB/c小鼠随机分为模型组(等体积0.9%氯化钠溶液)、阿司匹林组(200 mg/kg)和大蒜素高、中、低剂量组(40、20、10 mg/kg),每组10只;均灌胃给药,每天1次,连续3 d。末次给药1 h后给予小鼠腹腔注射0.7%冰醋酸溶液(0.2 mL)建模,记录建模15 min内其扭体反应次数。分组与给药同上,末次给药1 h后给予小鼠左后足底皮下注射1.5%甲醛溶液(25 μL)建模,记录建模后0~10 min(第Ⅰ时相)和10~60 min(第Ⅱ时相)时小鼠累计舔足时间。分组与给药同上,末次给药1 h后给予小鼠右耳廓正反两面均匀涂抹二甲苯(30 μL)建模,建模2 h后测定小鼠耳廓肿胀度,以两耳质量差值为耳廓肿胀度,并计算耳廓肿胀抑制率。50只BALB/c小鼠随机分为空白对照组(等体积0.9%氯化钠溶液)、模型组(等体积0.9%氯化钠溶液)和大蒜素高、中、低剂量组(40、20、10 mg/kg),每组10只;均灌胃给药,每天1次,连续3 d。末次给药20 min后给予小鼠足趾皮下注射1%角叉菜胶0.9%氯化钠溶液(30 μL)建模,分别于建模前及建模1、3、5 h后测定小鼠足趾容积,以建模前后小鼠足趾容积差值为足趾肿胀度;测定超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量以及总抗氧化能力(T-AOC)水平;采用Western blot法检测核转录因子κB(NF-κB)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)蛋白表达。结果:与模型组比较,阿司匹林组和大蒜素高、中剂量组小鼠扭体反应次数均显著减少;第Ⅰ时相时大蒜素高、中剂量组和第Ⅱ时相时阿司匹林组及大蒜素高、中剂量组小鼠累计舔足时间均显著缩短;阿司匹林组和大蒜素高剂量组小鼠耳廓肿胀度均显著降低;建模1、3 h后大蒜素高、中剂量组和建模5 h后大蒜素高剂量组小鼠足趾肿胀度均显著降低,差异均有统计学意义(P<0.05或P<0.01)。与空白对照组比较,模型组小鼠足趾肿胀组织中SOD、GSH-Px活性均显著减弱,MDA含量显著增加,T-AOC水平显著降低,NF-κB、TNF-α、IL-1β蛋白表达均显著增强,差异均有统计学意义(P<0.01);与模型组比较,大蒜素高剂量组小鼠足趾肿胀组织中SOD、GSH-Px活性均显著增强,MDA含量显著减少,且大蒜素高、中剂量组小鼠T-AOC水平均显著升高,同时大蒜素高剂量组小鼠足趾肿胀组织中NF-κB、TNF-α、IL-1β蛋白表达均显著减弱,差异均有统计学意义(P<0.05或P<0.01)。结论:大蒜素对模型小鼠炎性痛有一定的缓解作用,其机制与抗氧化应激反应和抑制NF-κB信号通路有关。
ABSTRACT: OBJECTIVE: To study the mechanism of anti-inflammatory pain effect of allicin in model mice. METHODS: Totally 50 BALB/c mice were randomly divided into model group (constant volume of 0.9% sodium chloride solution),aspirin group (200 mg/kg),allicin high-dose,medium-dose and low-dose groups (40,20,10 mg/kg),with 10 mice in each group. They were given relevant medicine intragastrically,once a day,for consecutive 3 d. One hour after last medication,they were given intraperitoneal injection of 0.7% glacial acetic acid solution (0.2 mL); the times of writhing response were recorded with in 15 min after modeling. Grouping and administration were same as above; 1 h after last medication,mice were given subcutaneous injection of 1.5% formaldehyde solution (25 μL) via left back toe; accumulative licking time of mice were recorded 0-10 min (time phaseⅠ) and 10-60 min (time phaseⅡ) after modeling. Grouping and administration were same as above; 1 h after last medication,mice were given xylene (30 μL) on both sides of right ear; the degree of auricular swelling of mice was determined 2 h after modeling. The mass difference of two ears was regarded as the degree of auricular swelling and then the inhibitory rate of swelling was calculated in mice. Totally 50 BALB/c mice were randomly divided into blank control group (constant volume of 0.9% sodium chloride solution),model group (constant volume of 0.9% sodium chloride solution) and allicin high-dose,medium-dose and low-dose groups (40,20,10 mg/kg),with 10 mice in each group. They were given relevant medicine intragastrically,once a day,for consecutive 3 d. Twenty minutes after last medication,mice were given subcutaneous injection of 1% carrageenan 0.9% sodium chloride solution (30 μL) via toe. Toe volume of mice was determined before modeling and 1,3,5 h after modeling. The difference of toe volume in mice was regarded as the degree of toe swelling. The activities of SOD and GSH-Px,contents of MDA,and level of T-AOC were determined. The expression levels of NF-κB,TNF-α and IL-1β protein were detected by Western blotting. RESULTS: Compared with model group,the times of writhing response were decreased significantly in aspirin group,allicin high-dose and medium-dose groups. The licking time of mice was shortened significantly in allicin high-dose and medium-dose group at time phaseⅠ, aspirin group,allicin high-dose and medium-dose at time phase Ⅱ. The degree of auricular swelling was decreased significantly in aspirin group and allicin high-dose group. The degree of paw swelling was decreased significantly in allicin high-dose and medium-dose groups 1,3 h after modeling, in allicin high-dose group 5 h after modeling,with statistical significance (P<0.05 or P<0.01). Compared with blank control group,the SOD and GSH-Px activities,level of T-AOC in paw swelling tissue of mice were decreased significantly in model group,while MDA content,the protein expression of NF-κB,TNF-α and IL-1β were increased significantly,with statistical significance (P<0.01). Compared with model group,SOD and GSH-Px activities in paw swelling tissue of mice were increased, while MDA content were decreased of allicin high-dose group and the activity of T-AOC in allicin high-dose and medium-dose groups were increased significantly; the protein expression of NF-κB,TNF-α and IL-1β in paw swelling tissue of mice were decreased significantly in allicin high-dose,and medium-dose groups,with statistical significance (P<0.05 or P<0.01). CONCLUSIONS: Allicin has certain anti-inflammatory pain effects,and its mechanism may be related to anti-oxidative stress and inhibition of NF-κB signaling pathway.
期刊: 2018年第29卷第18期
作者: 任亮,任翔,刘金宝,朱吾元,杜钢军
AUTHORS: REN Liang,REN Xiang,LIU Jinbao,ZHU Wuyuan,DU Gangjun
关键字: 大蒜素;炎性痛;氧化应激;核转录因子κB;肿瘤坏死因子α;白细胞介素1β
KEYWORDS: Allicin; Inflammatory pain; Oxidative stress; NF-κB; TNF-α; IL-1β
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