LncRNA-AK134503靶向miRNA-378调控肠缺血再灌注后肠粘膜细胞凋亡机制的研究

肠缺血再灌注（I/R）损伤是患者围术期死亡的原因之一。申请者既往证实肠粘膜细胞凋亡是肠I/R肠损伤的重要机制且Caspase-3是关键的执行者，新近又证实肠I/R后肠粘膜miRNA-378负性调节靶基因Caspase-3从而调控肠I/R后肠粘膜上皮细胞凋亡；进一步发现，LncRNA在肠I/R后肠粘膜表达明显上调，ceRNA生物学信息分析及qRT-PCR验证提示LncRNA-AK134503存在miRNA-378结合元件。据此，申请者提出科学假说：在肠I/R后的肠粘膜组织及肠粘膜上皮细胞中，LncRNA-AK134503表达上调且靶向结合miRNA-378，竞争性抑制miR-378对Caspase-3的负性调控，从而促进Caspase-3表达导致肠粘膜细胞凋亡。本课题假设LncRNA-AK134503是未来临床上防治肠I/R损伤的靶点，将通过系列离体及在体实验来证实该假设，具有重要科学意义。

Intestinal ischemia/reperfusion(I/R) is one of the leading causes for perioperative death of patient. The applicant previously demonstrated that intestinal mucosal apoptosis play a pivotal role in intestinal I/R-induced intestinal injury and Caspase-3 is the key executor for the generation of apoptosis. And the applicant recently found that miRNA-378 regulates intestinal mucosal epithelial apoptosis following intestinal I/R by targeting Caspase 3. Further, the applicant showed that the expression of LncRNA was upregulated in intestinal mucosa after intestinal I/R, and CeRNA biological information analysis and qRT-PCR verification showed that LncRNA - AK134503 includes binding domain of miR - 378. Based on the above findings, the applicant speculates that the upregulation of LncRNA-AK134503 expression in intestinal mucosa after intestinal I/R facilitates the generation of apoptosis via targeting miRNA-378 and competitively inhibiting the effect of miRNA-378 negative regulating Caspase 3. In the present study, a series of in vivo /in vitro experiments will be implemented to identify the above hypothesis. LncRNA-AK134503 could be taken as an important target for treating intestinal I/R in clinical settings.