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1.
目的 探讨细菌脂多糖(LPS)诱导活性小胶质细胞(MG)激活对少突胶质前体(preOLs)毒性作用.方法 2日龄SD大鼠随机分为假手术组和脑室周围白质软化(PVL)模型组,每组24只.脑立体定位仪下对PVL组新生大鼠经脑室注人LPS 1μg/g,建立感染型PVL新生大鼠动物模型;对假手术组新生大鼠经脑室注入相同体积的无菌PBS.于造模后第5天处死取脑,分别进行光镜下脑白质病理评估、硝酸还原法检测NO含量、还原比色法检测O-2含量、免疫组织化学染色检测过氧亚硝酸盐(ONOO-)含量以及OL前体的存活率.结果 与假手术组相比,LPS诱导可引起新生大鼠的脑白质严重损伤(Z=7.498,P=0.000),脑内O-2含量(42.822±3.600比187.717±8.566,t=26.907,P=0.000)明显增加,NO含量[(1.097±0.079)μmol/gprot比(2.878±0.183)μmol/gprot,t=34.728,P=0.000]、ONOO-含量[(0.000±0.000)%比(11.000±1.732)%]均显著增加,脑白质内O4阳性OL前体[(11.513±0.775)%比(3.353±0.442)%,t=16.013,P=0.000]大量减少.结论 从体内确认LPs诱导OL前体的死亡通路,是通过LPS诱导MG激活,促使生成大量NO、O-2和ONOO-,作用于OL前体,导致OL前体的死亡. 相似文献
2.
脑白质损伤是早产儿最常见的脑损伤形式,以少突胶质前体细胞(OPCs)损伤所造成的髓鞘脱失为特点。脑白质损伤后由于缺乏有效的治疗措施,幸存的患儿多遗留神经系统后遗症。细胞移植是近年来发现的对治疗白质损伤具有应用潜力的措施,目前细胞移植研究中常用的细胞是OPCs。OPCs兼有迁移和髓鞘化能力,是移植治疗最佳的种子细胞。研究发现OPCs移植不仅替代受损的细胞重建白质结构和功能,还能抑制神经元的凋亡,促进内源性神经干细胞的增殖,并促进血脑屏障的修复。但OPCs移植的临床应用还面临许多挑战,如有效性及致瘤风险、免疫排斥等安全性问题。该文就髓鞘发育、OPCs的获取、治疗机制及应用等方面做一综述,并分析了目前OPCs移植的挑战,以期为早产儿脑白质损伤的临床治疗提供新导向。 相似文献
3.
早产儿脑白质损伤病因复杂,可导致长期的神经认知行为缺陷,目前尚无特效的治疗手段。越来越多的研究表明,线粒体功能障碍在早产儿脑白质损伤发病过程中起重要作用,可能是脑白质发育障碍的常见亚细胞机制,涉及氧化应激、ATP合成减少、钙稳态失衡。文章将对线粒体在脑神经发育过程中的作用和造成其功能障碍的机制作一综述,希望能够通过保护线粒体功能对早产儿脑白质损伤进行及早干预,为改善存活早产儿神经发育结局提供参考。 相似文献
4.
目的 探究移植人少突胶质前体细胞(hOPCs)治疗早产儿脑白质损伤(WMI)的疗效。方法 将新生大鼠随机分为假手术组、模型组和移植组(n=10);模型组和移植组大鼠在3日龄时行右侧颈总动脉离断后缺氧2 h,制备WMI模型;从自然流产的11周人类胎儿脑中分离培养hOPCs,将hOPCs移植到WMI模型大鼠中。移植后3个月通过水迷宫实验评估大鼠神经功能,电镜观察大鼠髓鞘厚度和增生情况。结果 在Morris水迷宫定位航行实验中,模型组的逃避潜伏期比假手术组增加;与模型组相比,移植组的逃避潜伏期缩短(P < 0.05)。hOPCs移植在一定程度上减轻了90日龄WMI模型大鼠的认知功能障碍。电镜图像显示,移植hOPCs促进了WMI模型大鼠的大脑髓鞘再生。与假手术组相比,模型组的g-ratio(轴突总直径/纤维总直径)增加,提示髓鞘厚度减小;与模型组相比,移植组的g-ratio降低,提示髓鞘厚度增加(P < 0.05)。结论 鞘内移植hOPCs可以减轻WMI模型大鼠的神经损害并促进髓鞘再生。 相似文献
5.
《中国医学文摘(儿科学)》2006,(2)
目的通过向2日龄新生鼠腹腔注射LPS,建立脑白质损伤动物模型,并检测TLR4在这一损伤中表达变化,探讨其在LPS致WMD发生中的作用。方法2日龄新生鼠随机分为LPS组和对照组,分别腹腔注射LPS和等量生理盐水,观察脑白质区病理和细胞凋亡的变化,并检测注药后1h、2h、3h、4h、6h脑组织TLR4mRNA表达的变化。结果LPS组可见到明显的脑白质损伤,1h即有TLR4mRNA表达减低(P<0.01),2h达最低值,4h恢复基础的水平。结论2日龄新生鼠腹腔注射LPS可引起WMD,脑组织中TLR4在这一损伤早期即有明显的表达减低,提示TLR4参与了LPS所致的WMD,为早期诊断WMD提供了理论依据。 相似文献
6.
iNOS抑制剂阻断由细菌脂多糖诱导活性小胶质细胞对少突胶质细胞前体毒性作用的研究 总被引:1,自引:0,他引:1
目的 探讨由细菌脂多糖(lipopolysaccharide,LPS)诱导的活性小胶质细胞(MG)对少突胶质细胞(OL)前体的毒性作用及选择性iNOS抑制剂1400W对毒性作用的阻断效果.方法 取2日龄SD大鼠脑内MG和OL前体共培养,分为共培养对照组,共培养LPS组以及共培养LPS+1400W组.对共培养细胞经LPS 100 ng/ml诱导后48 h,分别应用硝酸还原比色法检测一氧化氮(NO)含量,免疫细胞染色法检测过氧亚硝酸盐(ONOO-)含量,Westem blot法检测诱生型一氧化氮合酶(Inducible Nitric Oxide Synthase,iNOS)蛋白合成量,Hochest 33342/PI荧光染色观察细胞凋亡形态学改变,以及流式细胞仪检测细胞凋亡率.结果 与共培养对照组比LPS可诱导培养细胞内NO含量[(82.27±3.41)tunol/L vs(167.86±9.87)μmol/L,t=8.593,P<0.01]、ONOO-含量[(6.14±1.27)×107/L vs(34.38±7.75)×107/L,t=5.892,P<0.01]以及iNOS蛋白合成量相对值[(0.18 4-0.027)vs.(0.79±0.068),t=9.26,P<0.01]明显增高,OL前体的凋亡率亦显著增加[(6.73 4±1.39)%vs.(24.77 4±2.05)%,t=12.619,P<0.01].应用1400W 10 μmol/L则可显著抑制因LPS诱导而增高的NO含量[(69.55±5.07)μmol/L,t=8.896,P<0.01]、ONOO-含量[(10.33±3.47)×107/L,t=14.96,P<0.01]以及iNOS蛋白的合成量(0.35±0.042,t=5.506,P<0.01),并显著降低了OL前体的细胞凋亡率[(11.8±2.06)%,t=7.715,P<0.01].结论 NO、iNOS以及ONOO-等物质在LPS诱导OL前体的死亡通路中扮演了重要角色,1400W通过选择性抑制iNOS,减少了NO以及ONOO-的生成,从而有效阻断了由LPS诱导活性MG对OL前体的毒性作用,提高了OL前体的存活率. 相似文献
7.
objective To explore the toxicity of LPS-induced activated microglia to preoligodendrocytes(preOLs)and the effect of 1400W,a selective inhibitor of inducible nitric oxide synthetase(iNOS),on the blockage of the toxicity.Methods Co-cultured micmglia and preOLs obtained from two-day-old Sprague-Dawley(SD) rats were divided into three groups:co-culture control group,co-culture LPS group and co-cultttre LPS plus 1400W group.After cultured ceils were induced by LPS (100 ng/ml)for 48 hours,the concentration of nitric oxide(NO) was measured by nitric acid-deoxidize-colorimetry,the level of peroxynitrite(ONOO-)was determined by immunocytochemistry,and the synthetic level of iNOS was deleted by Western blotting,respectively.The morphologic observation of apoptotic preOLs stained with Hoechst 33342/PI and the apoptotic rate of preOLs detected by flow cytometry were processed simultaneously.Data were analyzed with SPSS 11.0 software.Results Compared to co-culture control group,there was significant increase in levels of NO[(82.27±3.41)μmol/L vs(167.86±9.87)μmol/L,t=8.593,P<0.01],ONOO-[(6.14±1-1.27)x 107/L vs.(34.38±7.75)×107/L,t=5.892,P<0.01],and iNOS[(0.18±0.027) vs.(0.79±0.068),t=9.26,P<0.01] induced by LPS in co-culture LPS group,and with a higher apoptotic rate of preOLs[(6.73±1.39)% vs.(24.77±2.05)%,t:12.619,P<0.01].However.all levels of NO[(69.55±5.07)μmol/L,t=8.896,P相似文献
8.
objective To explore the toxicity of LPS-induced activated microglia to preoligodendrocytes(preOLs)and the effect of 1400W,a selective inhibitor of inducible nitric oxide synthetase(iNOS),on the blockage of the toxicity.Methods Co-cultured micmglia and preOLs obtained from two-day-old Sprague-Dawley(SD) rats were divided into three groups:co-culture control group,co-culture LPS group and co-cultttre LPS plus 1400W group.After cultured ceils were induced by LPS (100 ng/ml)for 48 hours,the concentration of nitric oxide(NO) was measured by nitric acid-deoxidize-colorimetry,the level of peroxynitrite(ONOO-)was determined by immunocytochemistry,and the synthetic level of iNOS was deleted by Western blotting,respectively.The morphologic observation of apoptotic preOLs stained with Hoechst 33342/PI and the apoptotic rate of preOLs detected by flow cytometry were processed simultaneously.Data were analyzed with SPSS 11.0 software.Results Compared to co-culture control group,there was significant increase in levels of NO[(82.27±3.41)μmol/L vs(167.86±9.87)μmol/L,t=8.593,P<0.01],ONOO-[(6.14±1-1.27)x 107/L vs.(34.38±7.75)×107/L,t=5.892,P<0.01],and iNOS[(0.18±0.027) vs.(0.79±0.068),t=9.26,P<0.01] induced by LPS in co-culture LPS group,and with a higher apoptotic rate of preOLs[(6.73±1.39)% vs.(24.77±2.05)%,t:12.619,P<0.01].However.all levels of NO[(69.55±5.07)μmol/L,t=8.896,P相似文献
9.
iNOS抑制剂阻断由细菌脂多糖诱导活性小胶质细胞对少突胶质细胞前体毒性作用的研究 总被引:1,自引:0,他引:1
objective To explore the toxicity of LPS-induced activated microglia to preoligodendrocytes(preOLs)and the effect of 1400W,a selective inhibitor of inducible nitric oxide synthetase(iNOS),on the blockage of the toxicity.Methods Co-cultured micmglia and preOLs obtained from two-day-old Sprague-Dawley(SD) rats were divided into three groups:co-culture control group,co-culture LPS group and co-cultttre LPS plus 1400W group.After cultured ceils were induced by LPS (100 ng/ml)for 48 hours,the concentration of nitric oxide(NO) was measured by nitric acid-deoxidize-colorimetry,the level of peroxynitrite(ONOO-)was determined by immunocytochemistry,and the synthetic level of iNOS was deleted by Western blotting,respectively.The morphologic observation of apoptotic preOLs stained with Hoechst 33342/PI and the apoptotic rate of preOLs detected by flow cytometry were processed simultaneously.Data were analyzed with SPSS 11.0 software.Results Compared to co-culture control group,there was significant increase in levels of NO[(82.27±3.41)μmol/L vs(167.86±9.87)μmol/L,t=8.593,P<0.01],ONOO-[(6.14±1-1.27)x 107/L vs.(34.38±7.75)×107/L,t=5.892,P<0.01],and iNOS[(0.18±0.027) vs.(0.79±0.068),t=9.26,P<0.01] induced by LPS in co-culture LPS group,and with a higher apoptotic rate of preOLs[(6.73±1.39)% vs.(24.77±2.05)%,t:12.619,P<0.01].However.all levels of NO[(69.55±5.07)μmol/L,t=8.896,P相似文献
10.
objective To explore the toxicity of LPS-induced activated microglia to preoligodendrocytes(preOLs)and the effect of 1400W,a selective inhibitor of inducible nitric oxide synthetase(iNOS),on the blockage of the toxicity.Methods Co-cultured micmglia and preOLs obtained from two-day-old Sprague-Dawley(SD) rats were divided into three groups:co-culture control group,co-culture LPS group and co-cultttre LPS plus 1400W group.After cultured ceils were induced by LPS (100 ng/ml)for 48 hours,the concentration of nitric oxide(NO) was measured by nitric acid-deoxidize-colorimetry,the level of peroxynitrite(ONOO-)was determined by immunocytochemistry,and the synthetic level of iNOS was deleted by Western blotting,respectively.The morphologic observation of apoptotic preOLs stained with Hoechst 33342/PI and the apoptotic rate of preOLs detected by flow cytometry were processed simultaneously.Data were analyzed with SPSS 11.0 software.Results Compared to co-culture control group,there was significant increase in levels of NO[(82.27±3.41)μmol/L vs(167.86±9.87)μmol/L,t=8.593,P<0.01],ONOO-[(6.14±1-1.27)x 107/L vs.(34.38±7.75)×107/L,t=5.892,P<0.01],and iNOS[(0.18±0.027) vs.(0.79±0.068),t=9.26,P<0.01] induced by LPS in co-culture LPS group,and with a higher apoptotic rate of preOLs[(6.73±1.39)% vs.(24.77±2.05)%,t:12.619,P<0.01].However.all levels of NO[(69.55±5.07)μmol/L,t=8.896,P相似文献
11.
先天性心脏病(congenital heart disease,CHD)是最常见的出生缺陷疾病.近年来,随着心脏外科技术的显著提升,复杂性CHD新生儿和婴幼儿的生存率已经明显提高.然而,神经性后遗症仍然常见并且高达25% ~55%.CHD术后大脑损伤最主要的是白质(white matter,WM)损伤.研究表明,以脑室周围WM软化病为特点的WM损伤常见于CHD婴幼儿尤其是心脏外科术后.既往人们认为这是由于术中体外循环和外科手术操作引起.然而,随着外科手术、医疗诊断技术的不断进步和基础研究的不断深入,人们发现CHD患儿WM损伤是术前、术中、术后多重因素综合作用的结果.这些患儿生长发育后期出现的运动障碍、注意力和学习等方面的缺陷给家庭和社会带来巨大经济负担,降低了人口素质.因此,探究CHD患儿WM损伤的原因、机制和防治方法成为近年CHD脑损伤研究热点,也可能成为未来进一步显著改善CHD患几神经发育损伤的重要研究方向. 相似文献
12.
少突胶质前体细胞移植治疗早产儿脑白质损伤大鼠模型 总被引:2,自引:1,他引:1
目的探讨少突胶质前体细胞(OPCs)移植对治疗早产儿脑白质损伤(WMI)模型大鼠的长期作用。方法将80只3日龄Sprague-Dawley大鼠随机分为假手术组、模型对照组、5 d脑室/白质移植组、9 d脑室/白质移植组、14 d脑室/白质移植组(n=10);除假手术组外其余各组行右侧颈总动脉离断并缺氧80 min制备早产儿WMI模型;采用孕10~12周人胚胎脑组织制备OPCs。各移植组分别在造模后5 d、9 d和14 d将3×105OPCs注入右侧脑室/脑白质中,待大鼠60日龄和90日龄时分别对各组行电镜下脑髓鞘评估和神经功能评估。结果电镜下,大鼠60日龄时各移植组髓鞘损害程度相比模型组略有改善;无论是与同组60日龄大鼠还是与同日龄模型组大鼠比较,90日龄时各移植组的髓鞘均明显增厚,结构破坏更少,其中14 d移植组变化最为明显;但不同移植时间脑室和白质移植组间的髓鞘损害程度未见有明显差异。60及90日龄各移植组大鼠的神经功能缺陷评分(m NSS)均高于假手术组,但均低于模型组(P0.05)。结论 OPCs移植可能对治疗早产儿WMI存在长期效应,延迟移植时间可能增强疗效。 相似文献
13.
Takashi Matsuoka Tomoyo Matsubara Kumiko Katayama Kanae Takeda Mayumi KogaAND Susumu Furukawa 《Pediatrics international》2001,43(5):453-457
BACKGROUND: Although infection is a frequent and important cause of morbidity and mortality in the neonatal period, evaluation of the immune system in cases of intrauterine infection is not easy. The subsets of T helper (Th) 1, which produce mainly interferon gamma (IFN-gamma), and Th2, which produce interleukin (IL) -4, have been implicated in the regulation of many immune responses. In this study, we investigated Th1 and Th2 subsets in the cord blood (CB) to evaluate the role of CB T cells in the intrauterine infections. METHODS: We used an intracellular cytokine-staining technique with determination by flow cytometry to study IFN-gamma-producing T cells and IL-4-producing T cells in the CB of six neonates with perinatal intrauterine infection and 17 uninfected neonates. RESULTS: The CB from neonates with intrauterine infections had more IFN-gamma-producing CD3+T cells than that from uninfected neonates. The percentage of CB IFN-gamma-producing CD3+T cells in the infected neonates correlated with the duration of membrane rupture before the onset of labor, but not with the level of C-reactive protein. The infected neonate born after the longest duration of membrane rupture showed an increased percentage of IL-4-producing CD3+T cells. CONCLUSIONS: Our results suggest that the increase of CB IFN-gamma and IL-4- producing T cells is part of the immune system directed against perinatal intrauterine infections. 相似文献
14.
Debillon T Gras-Leguen C Vérielle V Caillon J Roze JC Gressens P 《Acta paediatrica (Oslo, Norway : 1992)》2003,92(1):81-86
Aim: To evaluate the effects of maternal antibiotic treatment on fetal brain cell death in a rabbit intrauterine infection model. Methods: After Escherichia coli uterine-horn inoculation in 22 pregnant rabbits, followed at various times by ceftriaxone and caesarean section, cell death in white matter (histology and fragmented DNA staining) from fetuses killed at extraction was compared across groups using the Mantel-Haenszel test and Fisher's exact test for small numbers. Results: White matter cell death was consistently present at 48 h, with ceftriaxone initiation at 24 h (group 1), detectable at 84 but not 60 h, with ceftriaxone initiation at 12 h, and significantly reduced at 84 h with ceftriaxone initiation at 6 h (60% vs 100% in group 1, p 3 0.001, Fisher's exact test). Conclusion: Early maternal antibiotic therapy delays white matter cell death in rabbit fetuses exposed to intrauterine infection. This may provide a window for preventing white matter damage. 相似文献