Department of Neurology, Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, 318000, Zhejiang Province, China.
Department of Anesthesiology, Lishui Municipal Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, 323000, Zhejiang Province, China.
Inflammation. 2021 Jun;44(3):1035-1048. doi: 10.1007/s10753-020-01399-3. Epub 2021 Jan 4.
Acute cerebral infarction (ACI) possesses high mortality. Exosomes present in serum have potential application value in ACI diagnosis. This study investigated the mechanism of serum exosomes in ACI. Serum exosomes isolated from ACI patients and normal people were identified and then injected into the established middle cerebral artery occlusion (MCAO) rat model to evaluate cerebral injury and inflammation. Exosomal microRNA (miR)-27-3p expression was detected and interfered to analyze rat cerebral inflammation. The binding relationship between miR-27-3p and PPARγ was predicted and verified. The lipopolysaccharide (LPS)-treated microglia model was established and intervened with miR-27-3p to detect PPARγ, Iba-1, and inflammation-related factor expressions. After overexpressing PPARγ, rat cerebral inflammation was evaluated. The clinical significance of serum exosomal miR-27-3p in ACI was evaluated. Serum exosomes from ACI patients caused exacerbated MCAO rat cerebral injury and poor behavior recovery, as well as promoted cerebral inflammation. Serum exosomal miR-27-3p deepened rat brain inflammation. miR-27-3p targeted PPARγ to promote microglia activation and inflammation-related factor expressions in MCAO rats, and overexpressing PPARγ attenuated MCAO rat cerebral inflammation. Serum exosomal miR-27-3p promised to be a biomarker for ACI. We proved that serum exosomes from ACI patients aggravated ACI patient cerebral inflammation via the miR-27-3p/PPARγ axis.
急性脑梗死(ACI)具有较高的死亡率。血清中的外泌体在 ACI 诊断中具有潜在的应用价值。本研究探讨了血清外泌体在 ACI 中的作用机制。从 ACI 患者和正常人中分离血清外泌体,然后将其注入建立的大脑中动脉闭塞(MCAO)大鼠模型中,以评估脑损伤和炎症。检测外泌体 microRNA(miR)-27-3p 的表达,并进行干扰分析大鼠脑炎症。预测并验证 miR-27-3p 与 PPARγ 的结合关系。建立脂多糖(LPS)处理的小胶质细胞模型,并通过 miR-27-3p 进行干预,检测 PPARγ、Iba-1 和炎症相关因子的表达。过表达 PPARγ 后,评估大鼠脑炎症。评估血清外泌体 miR-27-3p 在 ACI 中的临床意义。ACI 患者的血清外泌体导致 MCAO 大鼠脑损伤加重和行为恢复不良,并促进脑炎症。血清外泌体 miR-27-3p 加深了大鼠脑炎症。miR-27-3p 靶向 PPARγ 促进 MCAO 大鼠小胶质细胞激活和炎症相关因子的表达,而过表达 PPARγ 则减轻 MCAO 大鼠脑炎症。血清外泌体 miR-27-3p 有望成为 ACI 的生物标志物。我们证明了来自 ACI 患者的血清外泌体通过 miR-27-3p/PPARγ 轴加重了 ACI 患者的脑炎症。