MicroRNA profiling of the intestine during hypothermic circulatory arrest in swine
MicroRNA profiling of the intestine during hypothermic circulatory arrest in swine
复制标题
猪低温停循环期间肠道的 MicroRNA 分析
DOI：
10.3748/wjg.v21.i7.2183
复制
发表时间：
2015-02-21
影响因子：
4.3
通讯作者：
Wu, Zhong-Kai
中科院分区：
文献类型：
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作者：
Lin, Wei-Bin;Liang, Meng-Ya;Wu, Zhong-Kai
目的：对低温循环停止（HCA）期间肠道microRNA （miRNA）表达的变化进行分析。方法：8头仔猪随机分为HCA组和假手术组。全麻条件下，HCA组猪行24℃低温体外循环，循环停搏80 min，取下交叉钳后再灌注180 min。SO组只行胸骨正中切开术。组织病理学分析用于检测粘膜损伤，使用含有306个独特引物集的Pick-and-Mix定制miRNA实时聚合酶链反应（PCR）面板对两组未合并的肠道样本进行检测。结果：经24℃HCA处理的动物肠黏膜表现出典型的2级或3级的缺血再灌注损伤。这种肠黏膜损伤表现为上皮下间隙和上皮层脱离固有层，并伴有绒毛缩短和不规则。相反，假手术动物的肠黏膜保持正常。总共有25个mirna在两组之间差异表达（HCA组中15个上调，10个下调）。其中，8个mirna （miR-122、miR-221-5p、miR-31、miR-421-5p、miR-4333、miR-499-3p、miR-542和let-7d-3p）显著失调（4个较高，4个较低）。miR-122在HCA组的表达较SO组显著升高（5.37倍），提示其可能在HCA诱导的粘膜损伤中发挥关键作用。结论：暴露于HCA可引起猪肠道miRNA失调和屏障功能障碍。这些改变的mirna可能与肠屏障的保护或破坏有关。
AIM: To perform a profiling analysis of changes in intestinal microRNA (miRNA) expression during hypothermic circulatory arrest (HCA).METHODS: A total of eight piglets were randomly divided into HCA and sham operation (SO) groups. Under general anesthesia, swine in the HCA group were subjected to hypothermic cardiopulmonary bypass at 24 degrees C followed by 80 min of circulatory arrest, and the reperfusion lasted for 180 min after cross-clamp removal. The counterparts in the SO group were only subjected to median sternotomy. Histopathological analysis was used to detect mucosal injury, and Pick-and-Mix custom miRNA real-time polymerase chain reaction (PCR) panels containing 306 unique primer sets were utilized to assay unpooled intestinal samples harvested from the two groups.RESULTS: The intestinal mucosa of the animals that were subjected to 24 degrees C HCA exhibited representative ischemic reperfusion injury of grade 2 or 3 according to the Chiu score. Such intestinal mucosal injuries, with the subepithelial space and epithelial layer lifting away from the lamina propria, were accompanied by shortened and irregular villi. On the contrary, the intestinal mucosa remained normal in the sham-operated animals. In total, twenty-five miRNAs were differentially expressed between the two groups (15 upregulated and 10 downregulated in the HCA group). Among these, eight miRNAs (miR-122, miR-221-5p, miR-31, miR-421-5p, miR-4333, miR-499-3p, miR-542 and let-7d-3p) were significantly dysregulated (four higher and four lower). The expression of miR-122 was significantly (5.37-fold) increased in the HCA group vs the SO group, indicating that it may play a key role in HCA-induced mucosal injury.CONCLUSION: Exposure to HCA caused intestinal miRNA dysregulation and barrier dysfunction in swine. These altered miRNAs might be related to the protection or destruction of the intestinal barrier.