摘要
目的 探讨微小RNA-124(miR-124)基于磷脂酰肌醇3激酶(PI3K)/丝氨酸苏氨酸激酶(Akt)通路对脓毒症大鼠肾组织炎症和氧化应激的影响。方法 将72只SD大鼠均分为假手术组(不做任何处理)、模型组(造模成功后不做任何处理)、miR-124-agomir组(miR-124高表达腺病毒载体处理)、agomir-NC组(阴性对照空载体处理)、LY294002组(PI3K/Akt抑制剂处理)、miR-124-agomir+LY294002组(miR-124高表达腺病毒载体和PI3K/Akt抑制剂处理)。除假手术组外,其余各组均采用盲肠结扎穿刺法建立脓毒症肾损伤模型,并于造模成功后按各组相应给药处理。观察各组大鼠行为变化、肾组织炎症细胞浸润现象;检测各组大鼠肾功能指标、肾组织细胞凋亡、肾组织miR-124、PI3K/Akt通路蛋白表达水平、氧化应激相关蛋白、炎症因子及凋亡相关蛋白的表达。结果 与假手术组比较,模型组大鼠肾组织坏死及炎症细胞浸润现象严重,血清肌酐和血尿素氮水平、细胞凋亡率、磷酸化(p)-PI3K/PI3K、p-Akt/Akt、磷酸化核转录因子(p-NF)-κB p65/NF-κB p65、肿瘤坏死因子-α、NF-E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、B细胞淋巴瘤2相关X蛋白、Caspase-3表达升高(P<0.05),miR-124、超氧化物歧化酶、谷胱甘肽过氧化氢酶蛋白表达降低(P<0.05)。与模型组比较,miR-124-agomir组大鼠肾组织上述指标变化明显改善(P<0.05);LY294002组大鼠肾组织上述指标变化进一步加重(P<0.05)。miR-124-agomir+LY294002组大鼠逆转miR-124-agomir组上述指标(P<0.05)。结论 miR-124通过抑制炎症、氧化应激和细胞凋亡来改善脓毒症大鼠肾损伤进程,其机制可能与激活PI3K/Akt通路,诱导Nrf2/HO-1途径活化有关。
Aim To investigate the effects of microRNA-124(miR-124)on renal tissue inflammation and oxidative stress in septic rats based on the phosphatidylinositol 3 kinase(PI3K)/serine-threonine kinase(Akt)pathway.Methods 72 SD rats were divided into sham surgery group(without any treatment),model group(without any treatment after successful modeling),miR-124 agomir group(treated with miR-124 high expression adenovirus vector),agomir NC group(negative control empty vector treatment),LY294002 group(treated with PI3K/Akt inhibitor),miR-124 agomir+LY294002 group(treated with miR-124 high expression adenovirus vector and PI3K/Akt inhibitor treatment).Except for the sham surgery group,all other groups were used cecal ligation and puncture to establish a sepsis kidney injury model,and after successful modeling,each group was treated with corresponding medication.Observe the behavioral changes and inflammatory cells infiltration in renal tissue of rats in each group.The renal function indexes,renal histiocyte apoptosis,expression levels of miR-124,PI3K/Akt pathway proteins,expression of oxidative stress related proteins,inflammatory factors and apoptosis related proteins were detected in each group.Results Compared with the sham surgery group,the model group showed severe renal tissue necrosis and inflammatory cells infiltration,with serum creatinine and blood urea nitrogen levels,cell apoptosis rate,phosphorylated PI3K/PI3K,p-Akt/Akt,and phosphorylated nuclear transcription factor(p-NF)-κB p65/NF-κB p65,tumor necrosis factor-α,NF-E2 related factor 2(Nrf2),heme oxygenase-1(HO-1),B-cell lymphoma 2 related X protein,and Caspase-3 increased(P<0.05),the expression of superoxide dismutase and glu-tathione catalase protein decreased(P<0.05).Compared with the model group,the changes in the above indicators in the renal tissue of rats in the miR-124 agomir group were significantly improved(P<0.05);The changes in the above indi-cators in the kidney tissue of rats in the LY294002 group further worsened(P<0.05).The miR-124 agomir+LY2940
作者
谭晓
黄建
刘向东
TAN Xiao;HUANG Jian;LIU Xiangdong(Department of Critical Care Medicine,Affiliated Minda Hospital,Hubei Minzu University,Enshi 445000,Hubei,China)
出处
《中南医学科学杂志》
CAS
2023年第3期349-354,共6页
Medical Science Journal of Central South China
基金
湖北省卫计委指导性项目(WJ2017F126)。
