电针百会、神庭对脂多糖诱导的抑郁样小鼠行为及海马NOD样受体蛋白3炎症小体的影响

Efficacy of electroacupunctureat Baihui(GV20)and Shenting(GV24)on lipopolysaccharide-induced depression-like behavior in mice and its effect on NOD-like receptor protein 3inflammasome in hippocampal region

目的观察电针百会、神庭对脂多糖(LPS)诱导的抑郁样小鼠行为及NOD样受体蛋白3炎症小体(NLRP3)的影响。方法将32只雄性C57BL/6小鼠随机分为对照组、模型组、电针组和氟西汀组,每组8只。模型组、电针组、氟西汀组小鼠每日予腹腔注射脂多糖(LPS)建立急性抑郁小鼠模型,连续5天。在造模同时,电针组每日予百会、神庭穴电针治疗,氟西汀组每日予氟西汀20 mg/kg灌胃,对照组、模型组小鼠每日予等容积0.9%氯化钠注射液灌胃,连续5天。干预结束后采用旷场实验、强迫游泳实验进行行为学测试,评估各组小鼠行为学变化。采用蛋白免疫印迹法(Western Blot)检测海马组织NLRP3、半胱天冬酶-1(Caspase-1)、白细胞介素1β(IL-1β)的蛋白表达。结果旷场实验结果显示,各组小鼠的总运动总路程比较差异无统计学意义(P<0.05)。与对照组比较,模型组小鼠中央区域停留时间明显缩短(P<0.05);与模型组比较,电针组、氟西汀组小鼠中央区域停留时间均明显延长(P<0.05);与电针组比较,氟西汀组小鼠中央区域停留时间延长(P<0.05)。强迫游泳实验结果显示,与对照组比较,模型组小鼠不动时间明显延长(P<0.05);与模型组比较,电针组、氟西汀组小鼠不动时间均缩短(P<0.05);与电针组比较,氟西汀组小鼠不动时间缩短(P<0.05)。Western Blot结果显示,与对照组比较,模型组海马NLRP3、Caspase-1、IL-1β蛋白表达均升高(P<0.05);与模型组比较,电针组、氟西汀组NLRP3、Caspase-1、IL-1β蛋白表达均降低(P<0.05);电针组与氟西汀组组间比较差异无统计学意义(P>0.05)。结论电针治疗可显著改善LPS诱导的小鼠抑郁样行为,其作用机制可能与抑制NLRP3信号通路的活化有关。

Objective To observe the efficacy of electroacupuncture(EA)at Baihui(GV20)and Shenting(GV24)on lipopolysaccharide(LPS)-induced depression-like behavior in mice and its effect on NOD-like receptor protein 3(NLRP3)inflammasome in hippocampal region.Methods Thirty-two male C57BL/6 mice were randomly divided into 4 groups:control group,model group,EA group and fluoxetine group,with 8 mice in each group.In addition to the control group,mice in the other three groups were intraperitoneally injected with LPS daily to establish acute depression mice model for 5 days.Meanwhile,the EA group received EA at Baihui(GV20)and Shenting(GV24)daily,the fluoxetine group received 20 mg/kg fluoxetine by gavage daily,and the control and model groups received an equal volume of 0.9%sodium chloride injection by gavage.Behavioral tests were performed to evaluate the behavioral changes of mice through open field test(OFT)and forced swimming test(FST).The expression of NLRP3 inflammasome in hippocampal region,caspase-1,and interleukin 1β(IL-1β)was detected using Western Blot.Results The results of OFT showed that the total movement distance of mice in each group was comparable(P>0.05).Compared with the control group,the time spent in the center in the model group was significantly shortened(P<0.05),which in the EA group was significantly longer than the model group(P<0.05),and the fluoxetine group was significantly longer than the EA group(P<0.05).The results of FST showed that the immobility time in the model group was significantly longer than that of the control group(P<0.05);in the comparison of the other three groups except the control group,the immobility time was the shortest in the fluoxetine group,followed by the EA group,and the model group(all P<0.05).Western Blot results showed that the expressions of NLRP3,Caspase-1,and IL-1βin the model group were significantly higher than those in the control group(P<0.05),which in the EA group and the fluoxetine group were significantly lower than those in the model group(P<0.05),and with no statistically significant difference between the EA group and the fluoxetine group(P>0.05).Conclusion EA treatment can significantly improve LPS-induced depression-like behavior in mice by inhibiting the activation of the NLRP3 signaling pathway.