【摘要】：目的探究魚腥草素鈉(sodium houttuyfonate,SH)對(duì)大鼠脊髓損傷(spinal cord injury,SCI)早期的神經(jīng)保護(hù)作用及與小膠質(zhì)/巨噬細(xì)胞表型M1型和M2型轉(zhuǎn)化的關(guān)系。方法首先,判定SH的最佳藥物劑量,40只SD雌性大鼠被隨機(jī)分為假手術(shù)組,實(shí)驗(yàn)組(根據(jù)給藥質(zhì)量濃度不同分為低(0.06 g·kg~(-1)·d~(-1))、中(0.12 g·kg~(-1)·d~(-1))、高(0.24 g·kg~(-1)·d~(-1))3個(gè)劑量組)和模型組。連續(xù)灌胃給藥7 d,余下各組給予生理鹽水對(duì)照。BBB評(píng)分檢測(cè)大鼠后肢運(yùn)動(dòng)功能;尼氏染色及免疫染色用于觀察前角神經(jīng)元結(jié)構(gòu)和生理功能并計(jì)數(shù)其數(shù)量;綜合上述結(jié)果判定SH的最佳治療劑量。其次,為探究其神經(jīng)保護(hù)的可能機(jī)制,24只SD雌性大鼠被隨機(jī)分為假手術(shù)組、SH最佳劑量組、模型組,各8只;免疫熒光及Western blot檢測(cè)各組炎癥因子(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)以及小膠質(zhì)/巨噬細(xì)胞極化標(biāo)志物iNOS(M1型)和Argi1(M2型)的表達(dá)。結(jié)果中、高劑量SH能無(wú)差別的改善SCI后大鼠的后肢運(yùn)動(dòng)功能,保留SCI處神經(jīng)元的正常結(jié)構(gòu)和部分生理功能和減少SCI后運(yùn)動(dòng)神經(jīng)元的丟失;綜合上述結(jié)果判定中劑量(0.12 g·kg~(-1)·d~(-1))為本實(shí)驗(yàn)的最佳劑量。與模型組相比,中劑量組中iNOS+細(xì)胞數(shù)量和蛋白iNOS、TNF-α、IL-1β、P-JNK/JNK、P-ERK/ERK、P-P38MAPK/P38MAPK的表達(dá)減少,而Argi+細(xì)胞數(shù)量和蛋白Argi的表達(dá)則增加。結(jié)論 SH對(duì)SCI大鼠具有一定的神經(jīng)保護(hù)作用,其保護(hù)作用可能是通過(guò)抑制SCI后MAPK信號(hào)通路的激活,促進(jìn)M1型小膠質(zhì)/巨噬細(xì)胞向M2型轉(zhuǎn)化,減輕其所介導(dǎo)的神經(jīng)炎癥反應(yīng)。
[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- 偽, 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- 偽, IL-1 尾, P 鈮，

本文編號(hào)：2503686