间充质细胞外泌体促进小鼠胰岛内皮细胞血管生成的研究

目的探讨间充质细胞（MSC）外泌体对低氧条件下胰岛内皮细胞（MS-1）血管生成的影响。方法 MSC无血清低氧条件培养48 h,超滤离心法富集条件培养基中的外泌体,采用电镜和Western Blot的方法进行鉴定;通过血管形成试验比较分析不同条件下:常氧培养组（NOR组,21%O2、5%CO2）、低浓度氧培养组（HYP组,2%O2、5%CO2）、外泌体+低浓度氧共培养组（HYP+EXO组,2%O2、5%CO2）,MS-1细胞的血管形成能力;image J软件分析血管形成长度;PCR、Q-PCR检测血管内皮生长因子（VEGF） RNA水平的表达,Western Blot检测VEGF、HIF1α蛋白水平表达以及mTOR信号通路激活情况。采用单因素方差分析和SNK-q检验统计学分析。结果超滤离心法富集的MSC条件培养基中的外泌体,大小为30～100 nm,表达CD9,CD63,CD81等外泌体表面标志物;血管形成试验结果显示,低氧促进MS-1血管生成,HYP+EXO组形成明显的血管网状结构;HYP+EXO组血管形成相对长度（2386.0±137.7）像素与NOR组（393.3±174.2）像素和HYP组（1467.0±230.0）像素相比增强,差异有统计学意义（t=12.30,P=0.0065;t=15.74,P=0.0040）; PCR结果显示,HYP+EXO组VEGF相对表达量（20.26±9.972）较常氧对照组（1.000）和低氧组（6.521±3.501）均增强,差异有统计学意义（t=5.462,P=0.0009;t=4.238,P=0.0038）;同时,Western Blot结果显示VEGF蛋白水平表达升高,HIF1-α表达上调,mTOR发生磷酸化。结论 MSC外泌体可促进低氧条件下的小鼠胰岛内皮细胞血管生成。MSC外泌体可能通过上调HIF1-α,调节VEGF表达,激活mTOR信号通路,促进胰岛内皮细胞血管生成。国家自然科学基金青年项目(81601618);;福建省自然科学基金面上项目(2016J01582、2016J01580、2018J01349);;福建省科技创新联合资金重大项目(2017Y9127

骨髓间充质细胞联合PDMS支架构建移植胰岛微环境的实验研究

目的为了提高移植胰岛的活性和功能,构建适合移植胰岛生存的微环境。方法采用聚二甲基硅氧烷(PDMS)和氯化钠晶体构建三维支架,联合骨髓间充质细胞(MSCs)、纤维蛋白和胰岛共同构建迷你\"人工胰腺\"。采用链脲佐菌素(STZ)诱导的糖尿病大鼠移植模型评价效果,将\"人工胰腺\"移植到糖尿病大鼠大网膜内,对照组行假手术,术后隔天监测移植大鼠血糖水平;数据采用t检验和曼-惠特尼U检验。结果用PDMS构建的三维巨孔支架,支架内可见大量不规则孔洞空间。胰岛和MSCs可成功装载入支架内,HE染色结果显示,支架孔内存在胰岛,胰岛周围包绕有MSCs。糖尿病大鼠大网膜内移植结果显示,移植后各时间点(1,3,5,7 d),\"人工胰腺\"移植组糖尿病大鼠血糖水平分别为(278.70±86.06) mg/dl、(323.50±44.29) mg/dl、(283.30±74.00) mg/dl、(304.80±13.33) mg/dl,较假手术对照组(606.00±52.40) mg/dl、(589.70±55.78) mg/dl、(615.00±54.84) mg/dl、(630.30±48.17) mg/dl均降低,差异具有统计学意义(t=7.96、9.15、8.82,U=0.00,P均<0.01)。结论 MSCs联合PDMS三维支架构建的微环境,可为移植胰岛提供生存的环境,为临床开展胰岛移植提供新的策略

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies