Sheng Xiaoming, Yang Yang, Liu JiaJia, Yu Junbo, Guo Qingsong, Guan Wei, Liu Fan
Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Immunobiology. 2022 Mar;227(2):152188. doi: 10.1016/j.imbio.2022.152188. Epub 2022 Feb 9.
Splenic hemorrhagic shock is a typical emergency in surgery, seriously threatening human beings' life. Emerging evidence shows that microRNAs (miRNAs) are closely related to inflammation and immunity in the body. However, the detailed effects and underlying mechanisms of miRNAs on the immune function of splenic hemorrhagic shock have not been revealed yet. In the present study, we construct the rat hemorrhagic shock model, and the rats are further cured with splenic blood transport clipping recanalization (SBTCR). MiR-18b-5p was highly expressed in the spleen of hemorrhagic shock rats detected by the qRT-PCR assay. Functionally, down-regulation of miR-18b-5p notably inhibited the levels of SOD1, iNOS and IL-6 in macrophages isolated from splenic tissues detected by qRT-PCR and ELISA assays. In addition, inhibition of miR-18b-5p significantly decreased the M1/M2 ratio of macrophages. Besides, knockdown of miR-18b-5p obviously reduced the Th1/Th2 ratio of CD4 T cells. Moreover, HIF-1α was predicted as a target gene of miR-18b-5p, which was further confirmed by dual-luciferase reporter assay, and HIF-1α was negatively associated with miR-18b-5p. Furthermore, overexpression of HIF-1α partially restored the effects of miR-18b-3p on inflammation and immunity in macrophages. Taken together, miR-18b-5p may be a novel therapeutic candidate target in splenic hemorrhagic shock treatment.
脾出血性休克是外科典型的急症，严重威胁人类生命。新出现的证据表明，微小RNA（miRNA）与体内炎症和免疫密切相关。然而，miRNA对脾出血性休克免疫功能的具体作用及潜在机制尚未阐明。在本研究中，我们构建了大鼠出血性休克模型，并采用脾血运阻断再通术（SBTCR）对大鼠进行进一步治疗。通过qRT-PCR检测发现，miR-18b-5p在出血性休克大鼠脾脏中高表达。在功能上，通过qRT-PCR和ELISA检测发现，下调miR-18b-5p可显著抑制从脾组织分离的巨噬细胞中SOD1、iNOS和IL-6的水平。此外，抑制miR-18b-5p可显著降低巨噬细胞的M1/M2比值。此外，敲低miR-18b-5p可明显降低CD4 T细胞的Th1/Th2比值。此外，HIF-1α被预测为miR-18b-5p的靶基因，双荧光素酶报告基因检测进一步证实了这一点，且HIF-1α与miR-18b-5p呈负相关。此外，过表达HIF-1α可部分恢复miR-18b-3p对巨噬细胞炎症和免疫的影响。综上所述，miR-18b-5p可能是脾出血性休克治疗中的一个新的治疗候选靶点。
