MicroRNA-146a: A Comprehensive Indicator of Inflammation and Oxidative Stress Status Induced in the Brain of Chronic T2DM Rats.
MicroRNA-146a: A Comprehensive Indicator of Inflammation and Oxidative Stress Status Induced in the Brain of Chronic T2DM Rats.
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DOI：
10.3389/fphar.2018.00478
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发表时间：
2018
影响因子：
5.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Xie Y;Chu A;Feng Y;Chen L;Shao Y;Luo Q;Deng X;Wu M;Shi X;Chen Y
目的：研究表明高血糖引起的炎症和氧化应激与miR-146a的改变密切相关。在这里，我们研究了miR-146a在慢性T2 DM大鼠脑内介导炎症和氧化应激中的作用。方法：以高脂高糖饲料喂养6周后，给予链脲佐菌素(STZ)35 mg/kg，建立慢性T2 DM动物模型。H&E染色观察大鼠海马区的形态损害。免疫印迹法检测炎症介质(COX-2、肿瘤坏死因子-α、IL-1β)和抗氧化蛋白(NRF2、HO-1)的表达。用相应的活性检测试剂盒检测丙二醛和超氧化物歧化酶水平。采用实时定量聚合酶链式反应(qRT-PCR)检测p22Phox和miR-146a的表达水平。免疫印迹和定量逆转录聚合酶链式反应检测IRAK1、TRAF6和NF-κBp65的表达。采用Pearson相关分析探讨miR-146a与炎症介质及氧化应激指标的相关性。结果：miR-146a的表达与炎症和氧化应激状态呈负相关。在cT2 DM大鼠脑组织中，炎症介质(COX-2、肿瘤坏死因子-α、IL-1β)和氧化应激指标(丙二醛、p22Phox)的表达增加，与miR-146a的表达呈负相关。而cT2 DM大鼠脑内抗氧化蛋白(NRF2、HO-1、SOD)水平降低，且与miR-146a水平呈正相关。CT2 DM大鼠脑内NF-κB p65及其特异性调节因子(IRAK1和TRAF6)的表达增加，可能被miR-146a抑制。结论：炎症和氧化应激状态的增加与cT2 DM大鼠脑损伤密切相关，且与miR-146a的表达呈负相关。因此，miR-146a可作为慢性T2 DM大鼠脑内炎症和氧化应激状态的阴性综合指标。
Objective: It was demonstrated that inflammation and oxidative stress induced by hyperglycemia were closely associated with alteration of miR-146a. Here, we investigated the role of miR-146a in mediating inflammation and oxidative stress in the brain of chronic T2DM rats. Methods: The chronic T2DM (cT2DM) models were induced by intraperitoneal administration of STZ (35 mg/kg) after being fed a high-fat, high-sugar diet for 6 weeks. H&E staining was conducted to observe the morphological impairment of the rat hippocampus. The expressions of inflammatory mediators (COX-2, TNF-α, IL-1β) and antioxidant proteins (Nrf2, HO-1) were measured by western blot. The levels of MDA and SOD were detected by the respective activity assay kit. The levels of p22phox and miR-146a were examined by quantitative real-time PCR (qRT-PCR). The expressions of IRAK1, TRAF6 and NF-κB p65 were measured by western blot and qRT-PCR. Pearson correlation analysis was performed to investigate the correlations between miR-146a and inflammatory mediators as well as oxidative stress indicators. Results: The expression of miR-146a was negatively correlated with inflammation and oxidative stress status. In the brain tissues of cT2DM rats, it was observed that the expressions of inflammatory mediators (COX-2, TNF-α, IL-1β) and oxidative stress indicators including MDA and p22phox were elevated, which were negatively correlated with the expression of miR-146a. While, the antioxidant proteins (Nrf2, HO-1, SOD) levels decreased in the brain of cT2DM rats, which were positively correlated with the miR-146a level. The expressions of NF-κB p65 and its specific modulators (IRAK1&TRAF6) were elevated in the brain of cT2DM rats, which might be inhibited by miR-146a. Conclusion: Our results implied that increased inflammation and oxidative stress status were associated with brain impairment in cT2DM rats, which were negatively correlated with miR-146a expression. Thus, miR-146a may serve as a negative comprehensive indicator of inflammation and oxidative stress status in the brain of chronic T2DM rats.
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