摘要
目的:观察海马CA1区注射米诺环素对坐骨神经缩窄性损伤(chronic constriction injury,CCI)大鼠海马小胶质细胞激活、Toll样受体2(Toll like receptor 2,TLR2)、Toll样受体4(Toll like receptor 4,TLR4)、IL-1β、TNF-α和诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)表达的影响。方法:成年SD大鼠随机分为3组(n=8):(1)sham组(假手术组+0.01 mol/L PBS)、(2)CCI组(CCI+0.01 mol/L PBS)、(3)CCI+米诺环素组。大鼠海马CA1区置管7 d后行坐骨神经结扎,CA1区注射0.01 mol/L PBS或米诺环素(2μg/μl),每日2次,连续7 d。于CCI术前1 d,术后1、3、5和7 d测定海马给药1 h后热缩足潜伏期(thermal withdrawal latency,TWL);术后第7 d取海马,荧光定量PCR检测Iba-1、TLR2、TLR4、IL-1β、TNF-α和i NOS m RNA表达;酶联免疫吸附试验测定海马IL-1β和TNF-α含量。结果:大鼠CCI术后即形成稳定的热痛敏,与假手术组相比,TWL明显缩短(P<0.01);与CCI组相比,海马CA1区注射米诺环素可明显延长CCI大鼠的TWL(P<0.05)。与假手术组相比,CCI大鼠海马Iba-1、TLR2、TLR4、IL-1β、TNF-α和i NOS m RNA表达明显上调(P<0.01);与CCI组相比,海马CA1区注射米诺环素几乎完全抑制海马Iba-1、TLR2、TLR4和TNF-αm RNA表达上调(P<0.01),仅部分阻断IL-1β和i NOS m RNA表达上调(P<0.05)。与假手术组相比,CCI大鼠海马IL-1β和TNF-α含量明显增多(P<0.01);与CCI组相比,注射米诺环素后几乎完全抑制海马TNF-α水平上升(P<0.01),仅部分抑制IL-1β水平上升(P<0.05)。结论:海马CA1区注射米诺环素可明显缓解CCI大鼠热痛敏症状,其机制可能与抑制海马小胶质细胞激活和TLR2、TLR4表达,进一步抑制IL-1β、TNF-α及i NOS表达有关。
Objective：The aim of this study is to investigate the effect of intra-CA1（cornu ammonis 1） adiministration of minocycline on thermal hyperalgesia and the expression of TLR2（Toll like receptor 2）,TLR4（Toll like receptor4）,IL-1β,TNF-α and i NOS（inducible nitric oxide synthase） in hippocampus of rats with chronic constriction injury（CCI） of the sciatic nerve.Methods：All rats were randomized into three groups（n = 8） ：（1） sham group（intra-hippocampal 0.01 mol/L PBS）,（2） CCI group（CCI,intra-hippocampal injection of 0.01 mol/L PBS）,（3） CCI ＋ minocycline group（intra-hippocampal injection of minocycline 2 μg/μl）.SD rats in all groups were bilaterally implanted withguide cannulas aimed to the CA1 region on 7 days before operation.For these ligated rats,0.01 mol/L PBS or minocycline（2 μg/μl） were intra-hippocampal injected twice per day for 7 d.TWL（thermal withdrawal latency） were evaluated before the surgery and on 1,3,5 and 7 d after surgery.The expression of Iba-1,TLR2,TLR4,IL-1β,TNF-α and i NOS m RNA in hippocampus was examined by real time RT-PCR on the 7 d after CCI operation.The content of IL-1βand TNF-α in hippocampus was examined by ELISA on the 7 d after CCI operation.Results：TWL in CCI group was significantly lower than that in the sham group after operation（P〈0.01）.Repeated administrated of minocycline markedly suppressed this decreased in TWL after nerve injury（P〈0.05）.Compared with sham group,the expression of Iba-1,TLR2,TLR4,IL-1β,TNF-α and i NOS m RNA in hippocampus were significantly increased in CCI rats（P〈0.01）.Compared with CCI group,intra-CA1 injection of minocycline obviously suppressed the increased expression of Iba-1,TLR2,TLR4 and TNF-α m RNA（P〈0.01） and partially blocked the increased expression of IL-1β and i NOS m RNA（P〈0.05）.Compared with sham group,the content of IL-1β and TNF-α in hippocampus were significantly increased in CCI rats（P〈0.01）.Compared with CCI group,intra-CA1 inj
作者
何丽
杨帆
杨俊娜
徐陶
徐瑞
许阿香
曾俊伟
He Li;Yang Fan;Yang Junna;Xu Tao;Xu Rui;Xu Axiang;Zeng Junwei(Department of Physiology,Zunyi Medical College,Guizhou Key Laboratory of Anesthesia and Organ Protection,Zunyi 563000,China)
出处
《神经解剖学杂志》
CAS
CSCD
北大核心
2018年第4期485-490,共6页
Chinese Journal of Neuroanatomy
基金
国家自然科学基金(1460266
31640040)
教育部新世纪优秀人才计划(NCET-13-1070)
贵州省遵义市科学技术联合基金(遵市科合社字2016-26号)
