發(fā)布時(shí)間：2018-07-23 11:30

【摘要】：目的:探討Rho激酶抑制劑法舒地爾(fasudil)聯(lián)合骨髓源神經(jīng)干細(xì)胞(bone marrow-derived neural stem cells,BM-NSCs)對(duì)實(shí)驗(yàn)性自身免疫性腦脊髓炎(experimental autoimmune encephalomyelitis,EAE)小鼠的神經(jīng)保護(hù)作用。方法:32只雌性C57BL/6小鼠(8~10周齡),用髓鞘少突膠質(zhì)細(xì)胞糖蛋白35-55(MOG35-55)免疫,制備EAE,隨機(jī)分為對(duì)照(dd H_2O)組、fasudil組、BM-NSCs組和fasudil+BM-NSCs組,并分別給予相應(yīng)處理。免疫后檢測(cè)小鼠臨床癥狀和相關(guān)神經(jīng)營(yíng)養(yǎng)因子的表達(dá),Image-Pro Plus 6.0軟件進(jìn)行陽性細(xì)胞計(jì)數(shù),Graph Pad Prism 5軟件統(tǒng)計(jì)分析。結(jié)果:與dd H_2O組比較,fasudil+BM-NSCs處理組明顯延遲小鼠的平均起病時(shí)間,降低最高臨床評(píng)分,并緩解EAE小鼠的臨床癥狀;fasudil組、BM-NSCs組和fasudil+BM-NSCs組中腦源性神經(jīng)營(yíng)養(yǎng)因子、膠質(zhì)細(xì)胞源性神經(jīng)營(yíng)養(yǎng)因子、神經(jīng)生長(zhǎng)因子、神經(jīng)營(yíng)養(yǎng)因子3和睫狀神經(jīng)營(yíng)養(yǎng)因子陽性細(xì)胞數(shù)均有不同程度的增加,其中,fasudil+BM-NSCs組上述神經(jīng)營(yíng)養(yǎng)因子的表達(dá)明顯多于dd H_2O組、fasudil組和BM-NSCs組(P0.01)。結(jié)論:Fasudil聯(lián)合BM-NSCs通過協(xié)同和疊加效應(yīng)促進(jìn)神經(jīng)營(yíng)養(yǎng)因子表達(dá),改善中樞神經(jīng)系統(tǒng)微環(huán)境,發(fā)揮神經(jīng)保護(hù)作用,從而緩解EAE的臨床癥狀。
[Abstract]:Aim: to investigate the neuroprotective effects of Rho kinase inhibitor fasudil (fasudil) combined with bone marrow-derived neural stem cells BM-NSCs on experimental autoimmune encephalomyelitis (experimental autoimmune) mice. Methods Thirty-two female C57BL/6 mice (810 weeks old) were immunized with oligodendrocyte glycoprotein 35-55 (MOG35-55). The mice were randomly divided into two groups: control group (d / H _ 2O) group, fasudil group (n = 10) and fasudil BM-NSCs group (n = 10). After immunization, the clinical symptoms and the expression of related neurotrophic factors in mice were detected by Image-Pro Plus 6.0 software. The positive cells were counted and analyzed by Graph Pad Prism5 software. Results: compared with the d H2O group, the treatment group of fasudil BM-NSCs significantly delayed the onset time, decreased the highest clinical score, and alleviated the clinical symptoms of BM-NSCs and fasudil BM-NSCs in BM-NSCs group and fasudil BM-NSCs group. The number of glial cell derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophic factor 3 (NGF) and ciliary neurotrophic factor (ciliary neurotrophic factor) positive cells increased in varying degrees. The expression of these neurotrophic factors in the fasudil BM-NSCs group was significantly higher than that in the d d H 2O group, fasudil group and BM-NSCs group (P0.01). Conclusion the expression of neurotrophic factor can be promoted by the synergistic and superimposed effect of BM-NSCs, the microenvironment of central nervous system can be improved and the neuroprotective effect can be brought into play so as to alleviate the clinical symptoms of EAE.
【作者單位】： 山西大同大學(xué)腦科學(xué)研究所;山西中醫(yī)學(xué)院神經(jīng)生物學(xué)研究中心;復(fù)旦大學(xué)華山醫(yī)院神經(jīng)病學(xué)研究所;托馬斯.杰弗遜大學(xué)神經(jīng)學(xué)系;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(No.81501198、No.81272163) 山西大同大學(xué)青年科研基金資助項(xiàng)目(No.2013Q11) 山西省回國(guó)留學(xué)人員重點(diǎn)科研資助項(xiàng)目(No.2014-重點(diǎn)7) 山西中醫(yī)學(xué)院“2011”培育計(jì)劃項(xiàng)目(No.2011PY-1)
【分類號(hào)】：R744.51

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