摘要
目的:探究治疗抑郁症中药新药参味宁郁片对抑郁模型大鼠行为学及海马Toll样受体4(TLR4)/髓样分化因子88(MyD88)信号通路介导免疫炎症的影响。方法:将44只雄性SD大鼠随机分为正常组、模型组、艾司西酞普兰组和参味宁郁片组。除正常组外,其余各组大鼠均采用慢性束缚应激(CRS)结合孤养建立抑郁症模型、持续接受21 d CRS刺激;艾司西酞普兰组每日在CRS应激前1 h给予艾司西酞普兰(30 mg·kg^(-1))灌胃给药;参味宁郁片组每日在CRS应激前1 h给予参味宁郁片(18 mg·kg^(-1))灌胃干预。实验前、后通过体质量变化、糖水实验、旷场实验测试,观察各组大鼠体质量、糖水偏好指数、水平运动评分、垂直运动评分变化;采用蛋白免疫印迹法(Western blot)检测海马TLR4,MyD88蛋白表达水平,应用酶联免疫吸附测定法(ELISA)检测血清炎性因子白细胞介素-1β(IL-1β),白细胞介素-10(IL-10)和肿瘤坏死因子-α(TNF-α)含量变化。结果:行为学结果显示,实验前,各组大鼠行为学基线水平具有一致性、各组均值差异无统计学意义。随着时间推移应激负荷增加,与正常组比较,模型组大鼠在接受CRS应激21 d后体质量、糖水偏好指数、水平运动评分和垂直运动评分均显著降低(P<0.01),与模型组比较,参味宁郁片组和艾司西酞普兰组大鼠体质量、糖水偏好指数、水平运动评分和垂直运动评分均显著升高(P<0.01),参味宁郁片表现出明显的抗抑郁效应;Western blot和ELISA结果显示,与正常组比较,模型组大鼠海马TLR4,MyD88蛋白及血清炎性因子IL-1β,TNF-α含量显著升高(P<0.01),血清IL-10含量降低(P<0.01),而与模型组比较,参味宁郁片组和艾司西酞普兰组有效逆转了应激诱导的海马TLR4,MyD88蛋白及血清炎性因子IL-1β含量显著升高、血清IL-10含量降低情况,差异具有统计学意义(P<0.01)。结论:治疗抑郁症中药新药参味宁郁片对慢性应激诱导
Objective:To explore the effects of Shenwei Ningyu pills(SNP),a new Chinese medicine for depression,on the immunoinflammatory response mediated by Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway in the hippocampus of rats exposed to chronic restraint stress(CRS).Method:Forty-four male Sprague Dawley rats were randomly enrolled into a normal group,a model group,an escitalopram group,and an SNP group.Except for the rats in the normal group,all rats were exposed to CRS and isolated rearing for 21 days continuously.Rats in the escitalopram group and the SNP group were administered with escitalopram(30 mg·kg^(-1))and SNP(18 mg·kg^(-1))one hour prior to CRS,respectively.The changes in body weight,sucrose preference index,horizontal movement scores,and vertical movement scores were observed by body weight assessment,sucrose preference test,and open field test.The expression of hippocampal TLR4 and MyD88 was detected by Western blot.The content of serum interleukin-1β(IL-1β),IL-10,and tumor necrosis factor-α(TNF-α)was detected by enzyme-linked immunosorbent assay(ELISA).Result:The results of the behavioral assessment showed that there was no significant difference in the changes of behavioral baselines among the groups before intervention.However,significant differences were found among the groups following different interventions.The body weight,sugar preference index,horizontal movement score,and vertical movement score of rats in the model group decreased after CRS for 21 days as compared with those in the normal group(P<0.01).The above indicators in the SNP group and the escitalopram group were higher than those in the model group(P<0.01),which indicated that SNP exerted an obvious antidepressant effect.The results of Western blot and ELISA showed that compared with the normal group,the model group showed elevated levels of hippocampal TLR4 and MyD88 and serum IL-1βand TNF-α(P<0.01)and dwindled serum IL-10(P<0.01),while SNP and escitalopram reversed the conditions in the m
作者
姜会梨
王雅欣
图娅
曾美桦
曾锦标
崔晓兰
李亚欢
高兴州
孙阳
郭姗姗
JIANG Hui-li;WANG Ya-xin;TU Ya;ZENG Mei-hua;ZENG Jin-biao;CUI Xiao-lan;LI Ya-huan;GAO Xing-zhou;SUN Yang;GUO Shan-shan(School of Acupuncture-Moxibustion and Tuina,Beijing University of Chinese Medicine,Beijing 100029,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;International Research Center for Mental Disorders,Beijing University of Chinese Medicine,Beijing 100029,China;Guangdong Siji Pharmaceutical Co.Ltd.,Shantou 515041,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第15期8-15,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家“重大新药创制”科技重大专项(2019ZX09301-005)。
