摘要
目的探究鱼腥草素钠(sodium houttuyfonate,SH)对大鼠脊髓损伤(spinal cord injury,SCI)早期的神经保护作用及与小胶质/巨噬细胞表型M1型和M2型转化的关系。方法首先,判定SH的最佳药物剂量,40只SD雌性大鼠被随机分为假手术组,实验组(根据给药质量浓度不同分为低(0.06 g·kg^(-1)·d^(-1))、中(0.12 g·kg^(-1)·d^(-1))、高(0.24 g·kg^(-1)·d^(-1))3个剂量组)和模型组。连续灌胃给药7 d,余下各组给予生理盐水对照。BBB评分检测大鼠后肢运动功能;尼氏染色及免疫染色用于观察前角神经元结构和生理功能并计数其数量;综合上述结果判定SH的最佳治疗剂量。其次,为探究其神经保护的可能机制,24只SD雌性大鼠被随机分为假手术组、SH最佳剂量组、模型组,各8只;免疫荧光及Western blot检测各组炎症因子(TNF-α、IL-1β)、P-JNK(phosphorylation c-Jun N-terminal kinase,P-JNK)、JNK、P-ERK(phosphorylation extracellular signal regulated kinase,ERK)、ERK、P-P38MAPK(phosphorylation P38 mitogen-activated protein kinase,P-P38MAPK)以及小胶质/巨噬细胞极化标志物iNOS(M1型)和Argi1(M2型)的表达。结果中、高剂量SH能无差别的改善SCI后大鼠的后肢运动功能,保留SCI处神经元的正常结构和部分生理功能和减少SCI后运动神经元的丢失;综合上述结果判定中剂量(0.12 g·kg^(-1)·d^(-1))为本实验的最佳剂量。与模型组相比,中剂量组中iNOS+细胞数量和蛋白iNOS、TNF-α、IL-1β、P-JNK/JNK、P-ERK/ERK、P-P38MAPK/P38MAPK的表达减少,而Argi+细胞数量和蛋白Argi的表达则增加。结论 SH对SCI大鼠具有一定的神经保护作用,其保护作用可能是通过抑制SCI后MAPK信号通路的激活,促进M1型小胶质/巨噬细胞向M2型转化,减轻其所介导的神经炎症反应。
The study was performed to investigate the neuroprotection effect of sodium houttuyfonate（SH）, thepolarization of microglia/macrophages and the microglia/macrophages meditated neuroinflammation in the earlyspinal cord injury（SCI） in rats. The model of SCI on rats was adopted, and the optimum dose of SH was confirmed byBBB scores, Nissl staining and the survival of motor neurons. The possible neuroprotection mechanisms of SH wasevaluated by exploring the expression of TNF-α, IL-1β, P-ERK, ERK P-JNK, JNK, P-P38 MAPK, P38 MAPK andthe M1 and M2 phenotypes microglia/macrophages. Data showed that SH had a certain neuroprotection in SCI ratsand the optimum therapeutic dose of SH in this study was medium dose SH 0.12 g·kg-1·d-1. Compared with SCIgroup, medium dose of SH treatment could significantly reduce the expression of TNF-α, IL-1β, P-JNK/JNK,P-ERK/ERK, P-P38 MAPK/P38 MAPK and iNOS, while upregulate the expression of Argi1. In conclusion, SH has a certain neuroprotective effect on early SCI in rats,which may be achieved by inhibiting the activation of MAPK signaling pathway, and then promoting the inflammatory M1 microglia/macrophages transformed to anti-inflammatory M2 cells, thus inhibiting the microglia/macrophages meditated neuroinflammatory after SCI.
作者
唐维
夏永智
刘敬贤
刘露
晏怡
TANG Weil XIA Yongzhi LIU Jingxian LIU Lu YAN Yi(Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China Department of Burn and Plastic Sugery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2017年第11期960-967,共8页
Immunological Journal
基金
国家自然科学基金(81100906)
重庆市自然科学基金(cstc2012jjA10055)
国家临床重点专科建设经费资助项目(财社[2011]170号)
关键词
脊髓损伤
鱼腥草素钠
神经保护
小胶质/巨噬细胞
Spinal cord injury
Sodium houttuyfonate
Neuroprotection
Microglia/macrophage
