低强度脉冲超声增效脂肪间充质干细胞源性外泌体修复 糖尿病小鼠皮肤创面的实验研究

目的：探讨低强度脉冲超声(LIPUS)对脂肪间充质干细胞源性外泌体(ADSCs-Exos)修复糖尿病皮肤创面的增效作用。方法：构建小鼠糖尿病皮肤创面模型并随机分为三组：对照组、ADSCs-Exos治疗组及LIPUS+ ADSCs-Exos治疗组,评估LIPUS对细胞摄取ADSCs-Exos的影响,比较各治疗组血管新生及皮肤创面修复情况。结果：与ADSCs-Exos治疗组相比,LIPUS可使HUVEC细胞对外泌体的摄取率提高9.77倍,活体成像显示LIPUS使小鼠皮肤创面区域的外泌体荧光分布更广、持续时间延长,差异均有统计学意义(均P＜0.01)。血管新生实验示LIPUS+ ADSCs-Exos 组创面区新生血管密度为35.12 ± 1.93,明显高于ADSCs-Exos治疗组及对照组(分别为20.25 ± 1.44和9.41 ± 0.98,P<0.05)。LIPUS+ ADSCs-Exos治疗组、ADSCs-Exos治疗组及对照组小鼠皮肤创面愈合的中位时间分别为10天、14天和19天,LIPUS+ ADSCs-Exos治疗组创面愈合最快、皮肤结构恢复最好,差异有统计学意义(P＜0.05)。结论：LIPUS能有效促进细胞对ADSCs-Exos的摄取,增强血管新生,加速糖尿病皮肤创面的修复。     

卵巢过度刺激综合征相关分子机制的研究进展

［摘要］　卵巢过度刺激综合征（OHSS）是辅助生殖技术中最严重的医源性并发症之一。在控制性促排卵过程中，部分患者会发生OHSS，影响到辅助生殖技术治疗的临床结局，增加患者的心理和经济负担，严重者危及生命安全。因此，解析探讨OHSS相关分子机制的研究对于临床预防和治疗有重大意义。该文就近年来与OHSS发生的相关分子机制研究进展作一综述。     

Emodin attenuates severe acute pancreatitis-associated acute lung injury by suppressing pancreatic exosome-mediated alveolar macrophage activation

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI; however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely, emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury, and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.     

肥大心肌细胞来源外泌体差异表达microRNA及其信号通路调节的初步研究

目的获得肥大心肌细胞来源外泌体与正常心肌细胞来源外泌体差异表达microRNA,并进行靶基因和信号通路分析,探讨差异表达microRNA调控心肌肥大的分子机制。方法取1~3天龄Wistar新生鼠心脏行原代心肌细胞培养,并分成两组,模型组用AngⅡ(1μmol/L)诱导心肌细胞肥大,对照组细胞未给予任何处理或加入培养液,分离纯化上述两组细胞外泌体,采用microRNA测序技术筛选差异表达microRNA,通过miRanda算法分析差异表达microRNA靶基因,并行KEGG pathway分析。结果与对照组比较,肥大心肌细胞来源外泌体有14个差异表达microRNA,其中13个microRNA上调(包括mmu-miR-2137、mmu-miR-5126、mmu-miR-690和10个新发现的microRNA),1个microRNA下调(P0.05)。通过miRanda算法得到差异表达microRNA的靶基因54条,采用排序前20的靶标基因及其相关microRNA构建局部网络图。经KEGG通路分析发现,差异表达microRNA参与了MAPK信号通路、PI3K-Akt信号通路、Wnt信号通路等的调节。结论肥大心肌细胞来源外泌体microRNA表达谱发生明显变化,并经靶基因调节MAPK等多种信号通路,进而影响心肌肥大的病理生理过程。     

外泌体源性miRNA在卒中及卒中后抑郁中的治疗作用及研究进展＊

外泌体是由不同种类细胞所分泌释放到细胞外间隙的小囊泡^［1］。外泌体广泛分布在各种体液中，内含有蛋白质、脂质及各种核酸类物质，包括信使RNA（mRNAs）、microRNAs（miRNAs）和其他非编码RNAs（ncRNAs），通过在细胞间运输这些物质达到调节受体细胞的作用。其中，miRNAs已被证明在脑卒中、卒中后抑郁等神经精神疾病中参与神经递质释放、神经元重塑、神经血管生成等过程，对于临床治疗有重要意义。脑卒中是一种复杂的脑血管疾病，具有较高的致死率和致残率。卒中后抑郁是卒中常见神经精神并发症，但目前使用的抗抑郁药物存在疗效不理想、副作用大等缺陷。外泌体源性miRNAs在脑卒中和神经修复中发挥着重要作用，对卒中及卒中后抑郁有潜在的治疗价值。本文探究外泌体源性miRNA在卒中及卒中后抑郁的作用机制，发掘其治疗价值，为相关的临床试验提供理论依据。     

外泌体在皮肤科的相关研究进展

外泌体是一种几乎所有细胞都可分泌的微小囊泡，由细胞经胞吐作用产生，并作用于靶细胞产 生效应。外泌体能够传递多种生物信号，参与多种生理、病理过程，还可以作为生物标记物、治疗药物、 药物载体、治疗靶点等。因此，外泌体在皮肤科学相关领域中具有重要意义。本文就外泌体及外泌体在皮 肤科疾病的相关研究进展作一综述，以期为皮肤科相关疾病的诊断和治疗提供新的策略与可能。     

Fusobacterium nucleatum-induced exosomal HOTTIP promotes gastric cancer progression through the microRNA-885-3p/EphB2 axis

Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.     

外泌体源性微 RNA与肛瘘术后创面愈合的研究进展

肛瘘作为常见的肛肠疾病，目前以手术治疗为主，但由于术后创面易被粪便污染，大多不做缝合，因此抑制创面炎症的发生以及促进创面的修复和愈合对于病人预后显得极为重要。近期有研究表明，外泌体在免疫调节、抑制炎症反应和修复受损组织等方面具有良好的应用前景，它是一种携带 DNA、RNA和蛋白质等多种生物活性物质的脂质双分子层囊泡，并通过自分泌或旁分泌的方式参与细胞之间的通信及各种生物学过程。其中，微 RNA(miRNA)作为一种非编码 RNA分子，以外泌体为载体，同样在各种生理病理过程中起到重要作用。因此，该研究旨在总结外泌体源性 miRNA对于肛瘘术后创面炎症和愈合的研究进展，以分析其潜在应用价值。