鱼腥草素钠对脊髓损伤后的神经保护作用及其机制初探
发布时间：2019-06-21 01:35
【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。
[Abstract]:Objective to investigate the neuroprotective effect of sodium houttuynia cordata (sodium houttuyfonate,SH) on early stage of spinal cord injury (spinal cord injury,SCI) in rats and its relationship with the transformation of microglia / macrophage phenotype M1 and M2. Methods the optimal dose of SH was determined. 40 female SD rats were randomly divided into three dose groups (0.06g kg~ (- 1) d1), (0.12g kg~ (- 1) d1),) and model group (0.24g kg~ (- 1) d1) according to the concentration of 0.06g kg~ (- 1) d1),. After 7 days of continuous administration, the rest groups were given saline control. BBB score was used to detect the motor function of hindlimb; Nissl staining and immunostaining were used to observe the structure and physiological function of anterior horn neurons and count their number. Combined with the above results, the best therapeutic dose of SH was determined. Secondly, in order to explore the possible mechanism of neuroprotection, 24 female SD rats were randomly divided into sham operation group, SH optimal dose group and model group with 8 rats in each group. The expression of inflammatory factors (TNF- 伪, IL-1 尾), 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), microglia / macrophage polarization markers iNOS (M1) and Argi1 (M2) were detected by immunofluorescence and Western blot. Results High dose SH could improve the motor function of hindlimb, preserve the normal structure and some physiological functions of neurons at SCI and reduce the loss of motor neurons after SCI, and determine that the middle dose (0.12g kg~ (- 1) d ~ (- 1) was the best dose in this experiment. Compared with the model group, the number of iNOS cells and the expression of protein iNOS,TNF- 伪, IL-1 尾, P 鈮，
本文编号：2503686
[Abstract]:Objective to investigate the neuroprotective effect of sodium houttuynia cordata (sodium houttuyfonate,SH) on early stage of spinal cord injury (spinal cord injury,SCI) in rats and its relationship with the transformation of microglia / macrophage phenotype M1 and M2. Methods the optimal dose of SH was determined. 40 female SD rats were randomly divided into three dose groups (0.06g kg~ (- 1) d1), (0.12g kg~ (- 1) d1),) and model group (0.24g kg~ (- 1) d1) according to the concentration of 0.06g kg~ (- 1) d1),. After 7 days of continuous administration, the rest groups were given saline control. BBB score was used to detect the motor function of hindlimb; Nissl staining and immunostaining were used to observe the structure and physiological function of anterior horn neurons and count their number. Combined with the above results, the best therapeutic dose of SH was determined. Secondly, in order to explore the possible mechanism of neuroprotection, 24 female SD rats were randomly divided into sham operation group, SH optimal dose group and model group with 8 rats in each group. The expression of inflammatory factors (TNF- 伪, IL-1 尾), 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), microglia / macrophage polarization markers iNOS (M1) and Argi1 (M2) were detected by immunofluorescence and Western blot. Results High dose SH could improve the motor function of hindlimb, preserve the normal structure and some physiological functions of neurons at SCI and reduce the loss of motor neurons after SCI, and determine that the middle dose (0.12g kg~ (- 1) d ~ (- 1) was the best dose in this experiment. Compared with the model group, the number of iNOS cells and the expression of protein iNOS,TNF- 伪, IL-1 尾, P 鈮，
本文编号：2503686
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