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Rapamycin在肝硬化大鼠小体积肝移植模型中对缺血再灌注损伤的保护作用及对肝脏星状细胞的激活和Rho-ROCK通路的研究

目的:在肝硬化大鼠小体积肝移植模型的基础上,研究药物Rapamycin对于肝硬化大鼠小体积肝移植术后供肝损伤所能起到的作用;探讨肝硬化大鼠小体积肝移植术后供肝损伤中,Rho-ROCK信号通路及肝星状细胞的激活所起的作用。通过动物实验初步揭示药物Rapamycin的作用及相关机理,为今后进一步的实验研究及该药物的临床应用提供初步的数据。方法:1.肝硬化大鼠小体积肝移植模型的建立 雄性健康Sprague-Dawley大鼠(330-380g)作为供体;雄性肝纤维化Sprague-Dawley大鼠(430-520g)作为受体。肝纤维化模型建立方法如下:雄性Sprague-Dawley大鼠,自出生后第六周起,每周两次皮下注射CCL4,剂量1ml·kg~(-1)·次~(-1)(溶于等体积橄榄油中),共持续8周。2.实验分组 实验分为两组,小肝对照组(n=30)、小肝用药组(n=30)。各组在每一时间点上各包括6对大鼠肝移植。于再灌注后6、2  (本文共41页) 本文目录 | 阅读全文>>

《Chinese Journal of Natural Medicines》2015年02期
Chinese Journal of Natural Medicines

Comparative analysis of rapamycin biosynthesis clusters between Actinoplanes sp. N902-109 and Streptomyces hygroscopicus ATCC29253

The present study was designed to identify the difference between two rapamycin biosynthetic gene clusters from Streptomyces hygroscopicus ATCC29253 and Actinoplanes sp. N902-109 by comparing the sequence and organization of the gene clusters. The biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus ATCC29253 was reported in 1995. The second rapamycin producer, Actinoplanes sp. N902-109, which was is...  (本文共9页) 阅读全文>>

《Journal of Huazhong University of Science and Technology(Medical Sciences)》2015年01期
Journal of Huazhong University of Science and Technology(Medical Sciences)

Rapamycin Protects Cardiomyocytes against Anoxia/Reoxygenation Injury by Inducing Autophagy through the PI3k/Akt Pathway

The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation(A/R) injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathway. We employed simulated A/R of neonatal rat ventricular myocytes(NRVM) as an in vitro model of ischemial/reperfusion(I/R) injury to the heart. NRVM were pretreated with four different concentrations of Ra...  (本文共6页) 阅读全文>>

《World Journal of Gastroenterology》2014年23期
World Journal of Gastroenterology

Inhibitory effects of rapamycin on the different stages of hepatic fibrosis

AIM:To investigate and compare the inhibitory effects of rapamycin in the different stages of liver fibrosis.METHODS:We performed bile duct ligation(BDL)in male Wistar rats(n=24).The experimental rats were classified into four groups:the BDL+/Rapa-group(untreated control,n=4),the BDL+/Rapa+group(treated14 d after BDL,n=8),the BDL+/Rapa++group(treated on the day after BDL,n=8),and the BDL-/Rapagroup(un-treated,sham-op...  (本文共9页) 阅读全文>>

广西大学
广西大学

Rapamycin对水牛成纤维细胞周期同期化以及核移植效率的影响

体细胞核移植技术尽管在许多哺乳动物已获得了成功,但克隆效率偏低仍然制约着该技术的应用。供体细胞周期调控是提高核移植效率的重要途径之一,因供体和受体细胞的细胞周期协调与克隆效率关系非常密切。Rapamycin是一种mTOR(mammalian target of rapamycin,mTOR)蛋白特异性抑制剂,能阻断细胞由G1至S期的进程,将细胞周期静止在G1期。因此,本研究探讨了Rapamycin和血清饥饿对BEF细胞周期和体细胞核移植胚胎发育能力的影响,旨在寻找一种合适的供体细胞同期化方法,为提高水牛体细胞克隆效率提供理论和技术依据。首先,比较了不同浓度Rapamycin(0,0.5,1,2,4μM)处理对BEF细胞周期和活力的影响。结果发现,11μM Rapamycin处理组细胞的活力及G0/G1期的比例显著高于对照组和其他试验组(P0.05)。比较Rapamycin处理BEF不同时间(0、48、72、96 h)对细胞周期的...  (本文共67页) 本文目录 | 阅读全文>>

江苏大学
江苏大学

IL-11-mTORC1-STAT3信号轴调节M-MDSC的分化发育

目的:我们前期在脓毒血症的临床和实验动物模型研究中发现IL-11能明显改善脓毒症患者临床症状,缩短康复时间和延长脓毒症小鼠的生存时间。动物实验证明在肝脏等器官中髓系来源的免疫抑制性细胞(myeloid derived suppressive cells,MDSC)数量明显增加,因此我们推测IL-11可能具有诱导MDSC分化发育的能力,在脓毒症早期具有炎症抑制作用,故而能防止脓毒症的进一步发展,从而缩短患者康复时间和延迟动物死亡时间。IL-11和IL-6具有类似的信号转导途径。已有文献报道IL-6能诱导MDSC的分化,且发现STAT3参与其信号转导,但是详细机制尚未阐明。我们通过生物信息学分析发现STAT3分子中存在着哺乳动物雷帕霉素靶蛋白复合物1(Mammalian Target of Rapamycin Complex 1,mTORC1)中Raptor的作用靶点TOS Motif,因此我们推测在IL-6/IL-11诱导MDSC...  (本文共74页) 本文目录 | 阅读全文>>