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101.
Parastoo Jangouk Thomas Dehmel Gerd Meyer Zu Hörste Andreas Ludwig Helmar C. Lehmann Bernd C. Kieseier 《Glia》2009,57(16):1765-1774
The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc. 相似文献
102.
增生性瘢痕中血管内皮细胞生物学功能的研究 总被引:2,自引:1,他引:1
目的 探讨增生性瘢痕中血管内皮细胞的生物学功能及其与瘢痕形成的关系。方法 取人增生性瘢痕组织和正常皮肤组织,进行组织学观察。分离和纯化2种标本中的血管内皮细胞,应用酶联免疫吸附测定法分别检测单个血管内皮细胞中转化生长因子β1,(TGF-β1)、成纤维细胞生长因子2(FGF2)、血小板源性生长因子(PDGF)、内皮素1(ET-1)和血管内皮生长因子(VEGF)的水平。结果光学显微镜下可见正常皮肤微血管数目较少;增生性瘢痕微血管数目增多,血管狭长扭曲甚至闭塞。透射电镜可见增生性瘢痕中毛细血管管腔狭窄,有内皮细胞脱落。增生性瘢痕中血管内皮细胞分泌TGF-β1、PDGF、ET-1、VEGF、FGF2的水平分别为(60±8)、(30±4)、(0.12±0.03)、(52±5)、(18.1±1.2)μg/个细胞,明显低于正常皮肤(P〈0.05)。结论 增生性瘢痕中血管内皮细胞生物学功能减退,可能与瘢痕中胶原的大量产生和缺氧有关。 相似文献
103.
作者用同位数前体参入法及透射与扫描电镜研究了平阳霉素(博莱霉素A_5)对HeLa细胞大分子生物合成及超微结构的影响。结果显示:平阳霉素能抑制HeLa细胞DNA,RNA和蛋白质的生物合成,对DNA的抑制作用强,ID_(50DNA)为42.77μg/ml。表现为:染色质减少,核内电子密度低,核仁分离及“核仁帽”形成,细胞表面微绒毛消失或变形,最终导致质膜破裂等。作者认为,细胞膜是否为此类药物作用的靶位值得进一步研究。 相似文献
104.
目的 研究转酪氨酸激酶C(tyrosine kinase C,TrkC)基因神经干细胞(neural stem cells,NSCs)移植治疗脊髓损伤的作用。方法 60只SD大鼠随机分成正常对照组(A组)、脊髓半切组(B组)、NSCs移植组(C组)、NSCs移植+神经营养素(NT)-3局部使用(D)组、转TrkC基WNSCs移植组(E组)和转TrkC基因NSCs移植+NT-3局部使用组(F组),每组10只。脊髓损伤后第9天进行细胞移植。各组大鼠在细胞移植后2个月,行体感诱发电位(SEP)和运动诱发电位(MEP)检查以及脊髓运动功能(BBB)评分。结果 细胞移植后2个月SEP和MEP发生潜伏期和峰峰波幅以及右后肢BBB评分的恢复均以下组最佳,与其他各组比较,差异有统计学意义(P< 0.05,0.01)。结论在局部给予的NT-3作用下,转TrkC基因NSCs能较好地促进损伤脊髓功能的恢复。 相似文献
105.
目的探讨大鼠脂肪来源间充质干细胞(MSC)对大鼠肝移植术后急性排斥反应的作用。方法分离、培养SD大鼠MSC,体外混合淋巴细胞培养(MLC)体系中,研究MSC对Wistar大鼠T细胞增殖的抑制作用。以SD与Wistar大鼠为供受体建立肝移植模型。随机分为MSC处理组与空白对照组,术后第7天检测肝功能、血清白细胞介素(IL)-2和白细胞介素(IL)-10水平、肝组织病理形态及肝细胞凋亡。结果体外MLC中,Wistar大鼠T细胞增殖明显受抑,抑制率为48.44%。实验组血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、IL-2、IL-10分别为(134.2±45.0)、(162.5±30.5)U/L、(30.6±5.4)μmol/L、(187.35±18.26)、(193.95±37.62)μg/L;对照组上述指标分别为(355.6±54.3)、(296.4±71.2)U/L、(145.7±28.6)μmoL/L、(295.73±57.15)、(75.12±11.23)μg/L,两组差异有统计学意义(P<0.05);病检提示实验组排斥反应较对照组明显减轻;脱氧脲核苷酸缺口末端标记(TUNEL)检测提示实验组肝细胞凋亡程度明显低于对照组(P<0.05)。结论供体来源MSC能明显抑制MLC体系中受体源T细胞的增殖,并能显著减轻大鼠肝移植术后急性排斥反应。 相似文献
106.
Min Zong Xinchun Yang Xiulan Liu Liang Shi Taifeng Liu 《岭南心血管病杂志(英文版)》2007,8(4):187-193
Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventricular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current (INa-Ca) and late INa in M region (deep subepicardial to midmyocardial). Studies from our laboratory have found a new repolarization current-nonselective cation current (NSCCs) existing in rabbit right ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp techniques. The permeability to Na , K , Li , Cs but not to Cl- indicating that it was a nonselective cation current. Gd3 (0.1 mmol/l) and La3 (0.1 mmol/l) can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to -80 mV, INs current density was (-0.44±0.05) PA/PF in endocardial cells, (-0.12±0.05) PA/PF in M cells and (-0.28±0.07) PA/PF in epicardial cells; and with repolarization to 30 mV, INs current density was (1.09±0.29) PA/PF in endocardial cells, (0.38±0.09) PA/PF in M cells and (0.91±0.32) PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias. 相似文献
107.
目的 观察共刺激分子阻断剂CD80单克隆抗体(CD80mAb)在协同未成熟树突细胞(imDC)诱导同种异体大鼠胰十二指肠移植免疫耐受中的作用。方法 建立糖尿病大鼠胰十二指肠移植动物模型;4E5杂交瘤细胞株BABIMC小鼠腹腔注射,抽取腹水,分离纯化后获得CD80mAb;分离供体大鼠骨髓来源DC细胞前体,经GM—CSF、IL-4体外刺激后。再加入IL-10共培养,鉴定为imDC;移植前7d,将2×10^6imDC经静脉途径注射至受体体内,同时分别给予生理盐水1ml、CD80mAb5mg连续14d。结果 四组受体大鼠移植后中位生存时间分别为12.7d、32.4d、50.2d、92.0d,实验组存活时间明显延长;组织学观察发现移植后7dCD80mAb+imDC组移植物形态尚完整,淋巴细胞浸润减少;混合淋巴细胞反应证实移植后7dCD80mAb+imDC组供受体间呈低反应性。结论 共刺激分子阻断剂CD80mAb能够协同imDC诱导受体T细胞对移植物的免疫耐受,降低宿主对移植物的急、慢性排斥反应,延长移植物的存活时间。 相似文献
108.
N S Davis 《The Prostate》1987,11(4):353-360
The finding of significant numbers of endocrine-paracrine (EP) cells in the prostate glands of guinea pigs and man suggests that these cells may be important in the regulation or modulation of prostatic function. Serotonin is a biogenic amine common to most prostatic EP cells. In order to extend current knowledge relating to these cells, an assay was developed using high-performance liquid chromatography to quantitate serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in guinea pig and human prostatic tissue extracts. Levels of serotonin and 5-HIAA in the guinea pig whole-gland preparation were 105.4 +/- 70.6 ng/g and 48.4 +/- 95.7 ng/g, respectively. Normal human prostatic tissue contained 1423.9 +/- 750.8 ng/g serotonin and 66.7 +/- 92.8 ng/g 5-HIAA. Recoveries ranged between 60 and 100%. The detection limits were 24 pg/injection for serotonin and 12 pg/injection for 5-HIAA. This assay provides an expeditious, specific and highly sensitive method for the simultaneous determination of monoamines in guinea pig and human prostatic tissue. 相似文献
109.
Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy. 相似文献
110.
复方积雪草有效组分对人肾小管上皮细胞补体C3表达的影响 总被引:2,自引:1,他引:1
目的:探讨复方积雪草有效组分——积雪草苷/大黄素干预肿瘤坏死因子-α(TNF-α)诱导的人肾近曲小管上皮细胞(HPTEC)补体C3 mRNA及蛋白的表达水平。方法:采用HPTEC,模型组TNF-α 10ng/ml诱导,治疗组在TNF-α诱导的同时,以不同浓度的积雪草苷、大黄素以及积雪草苷合大黄素进行干预,于24h后分别提取细胞RNA及上清,应用逆转录-聚合酶链反应(RT—PCR)和酶链免疫方法(ELISA)分别检测HPTEC C3 mRNA和蛋白的表达。结果:正常HPTEC具有C3 mRNA和蛋白表达,经TNF-α诱导后G表达明显上调,用不同浓度的积雪草苷、大黄素以及积雪草苷合大黄素干预后,C3 mRNA及蛋白水平表达出现不同程度的下调,呈一定的剂量依赖关系和协同作用。结论:复方积雪草有效组分能够抑制炎性细胞因子TNF-α上调所致的肾局部G过度产生。 相似文献