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Serum Exosomal microRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ
Inflammation ( IF 4.5 ) Pub Date : 2021-01-04 , DOI: 10.1007/s10753-020-01399-3
Zhinan Ye 1 , Jingchun Hu 2 , Hao Xu 1 , Bin Sun 1 , Yong Jin 3 , Yaping Zhang 1 , Jianli Zhang 4
Affiliation  

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.



中文翻译:


血清外泌体 microRNA-27-3p 通过靶向 PPARγ 加重急性脑梗死患者的脑损伤和炎症



急性脑梗塞(ACI)具有很高的死亡率。血清中存在的外泌体在 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。对从 ACI 患者和正常人中分离的血清外泌体进行鉴定,然后注射到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。检测并干扰外泌体微小RNA(miR)-27-3p表达来分析大鼠脑炎症。预测并验证了miR-27-3p与PPARγ之间的结合关系。建立脂多糖(LPS)处理的小胶质细胞模型,并用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。评估了血清外泌体 miR-27-3p 在 ACI 中的临床意义。 ACI 患者血清外泌体导致 MCAO 大鼠脑损伤加剧、行为恢复不良,并促进脑炎症。血清外泌体 miR-27-3p 加深了大鼠脑部炎症。 miR-27-3p靶向PPARγ促进MCAO大鼠小胶质细胞活化和炎症相关因子表达,过表达PPARγ可减轻MCAO大鼠脑部炎症。血清外泌体 miR-27-3p 有望成为 ACI 的生物标志物。我们证明,ACI 患者血清外泌体通过miR-27-3p/PPARγ 轴加重 ACI 患者脑部炎症。

更新日期:2021-01-04
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