miR-10a Ameliorates Renal and Myocardial Injury in Sepsis Through Regulation of PI3K/AKT Signaling

Chenglian Hu, Ying Yang, Lunhun Ye
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Abstract

miR-10a participates in the prognosis of patients with sepsis, which also influence multiple organs and cause damages to the kidney and myocardial tissues. This study intends to assess miR-10a’s role in sepsis-induced renal and myocardial injury. 50 Wistar rats were randomized into sham-operation group, model group, MiR-10a group, positive control group and PI3K/AKT-agonist group (n = 10) followed by analysis of the histopathological changes of myocardial and renal tissues, kidney injury, expression of renal GR-α and CK-MB/CK, levels of inflammatory factors (IL-10, IL-6, IL-1β and TNF-α) and the level of miR-10a, PI3K and AKT. Rats in model group and PI3K/AKT-agonist group exhibited highest pathological score of kidney injury, expression of CK-MB, CK and renal GR-α, followed by rats in positive control group and miR-10a group. Furthermore, model group and PI3K/AKT-agonist group showed the highest level of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-10), followed by positive control group and miR-10a group. Lowest miR-10a expression and highest mRNA levels of PI3K and AKT was detected in model group, PI3K/AKT-agonist group and positive control group, followed by miR-10a group. PI3K is a target of miR-10a. In conclusion, miR-10a alleviates the sepsis-induced renal and myocardial injury mainly by mediating the PI3K/AKT transduction pathway, indicating that miR-10a can be utilized as a target gene for sepsis treatment.
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miR-10a通过调节PI3K/AKT信号通路改善脓毒症的肾和心肌损伤
miR-10a参与脓毒症患者的预后,影响多脏器,对肾脏和心肌组织造成损害。本研究旨在评估miR-10a在脓毒症引起的肾脏和心肌损伤中的作用。将50只Wistar大鼠随机分为假手术组、模型组、MiR-10a组、阳性对照组和PI3K/AKT激动剂组(n = 10),分析心肌和肾脏组织病理变化、肾损伤、肾脏GR-α和CK- mb /CK表达、炎症因子(IL-10、IL-6、IL-1β、TNF-α)水平以及MiR-10a、PI3K、AKT水平。模型组和PI3K/ akt激动剂组大鼠肾损伤病理评分最高,CK- mb、CK和肾GR-α表达最高,阳性对照组和miR-10a组次之。模型组和PI3K/ akt激动剂组炎症因子(TNF-α、IL-1β、IL-6、IL-10)水平最高,阳性对照组和miR-10a组次之。模型组、PI3K/AKT激动剂组和阳性对照组miR-10a表达最低,PI3K和AKT mRNA水平最高,miR-10a组次之。PI3K是miR-10a的靶标。综上所述,miR-10a主要通过介导PI3K/AKT转导通路减轻脓毒症诱导的肾脏和心肌损伤,表明miR-10a可作为脓毒症治疗的靶基因。
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>12 weeks
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