Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Department of Respiration, The First Hospital of Lanzhou City, Lanzhou, Gansu 730050, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11942. Epub 2021 Mar 2.
Gestational diabetes mellitus (GDM) is a serious life‑threatening disease that affects the mother and fetus. However, the pathogenesis of GDM is still unclear. microRNAs (miRs) play vital roles in the regulation of various cell functions. The present study aimed to investigate the effects of miR‑875‑5p and thioredoxin reductase 1 cytoplasmic (TXNRD1) in GDM rats and analyze the associated underlying mechanism. A GDM rat model was induced using an intraperitoneal injection of streptozotocin. miR‑875‑5p knockdown plasmids or TXNRD1 knockdown plasmids were injected into the rats via the caudal vein. miR‑875‑5p and TXNRD1 expression in the serum were detected using reverse transcription‑quantitative PCR (RT‑qPCR) or western blot (WB) analyses. The fasting blood‑glucose (FBG), fasting serum insulin, triglyceride and high density lipoprotein levels were detected by specific commercial kits. The inflammatory response and the induction of oxidative stress were analyzed by assessing the expression of associated markers via WB, RT‑qPCR or commercial kits. The pancreatic and placental injuries were detected by hematoxylin and eosin staining. The results indicated that miR‑875‑5p expression levels were downregulated, whereas TXNRD1 levels were upregulated in GDM rats compared with normal pregnancy rats. miR‑875‑5p significantly regulated TXNRD1 expression in GDM rats. miR‑875‑5p silencing notably reduced FBG and insulin resistance, which was accompanied by reduced expression levels of blood lipid and pro‑inflammatory markers as well as reduced oxidative stress. However, the effects of miR‑875‑5p could be reversed by TXNRD1 silencing. Therefore, the present study indicated that miR‑875‑5p regulated IR and inflammation by targeting TXNRD1 in GDM rats. miR‑875‑5p and TXNRD1 may be considered as potential targets for treating GDM.
妊娠期糖尿病（GDM）是一种严重的危及生命的疾病，影响母亲和胎儿。然而，GDM 的发病机制尚不清楚。microRNAs（miRs）在调节各种细胞功能中发挥着重要作用。本研究旨在探讨 miR-875-5p 和硫氧还蛋白还原酶 1 细胞质（TXNRD1）在 GDM 大鼠中的作用，并分析其相关的潜在机制。通过腹腔注射链脲佐菌素诱导 GDM 大鼠模型。通过尾静脉向大鼠注射 miR-875-5p 敲低质粒或 TXNRD1 敲低质粒。采用逆转录-定量 PCR（RT-qPCR）或 Western blot（WB）分析检测血清中 miR-875-5p 和 TXNRD1 的表达。采用特定的商业试剂盒检测空腹血糖（FBG）、空腹血清胰岛素、甘油三酯和高密度脂蛋白水平。通过 WB、RT-qPCR 或商业试剂盒分析相关标志物的表达，以评估炎症反应和氧化应激的诱导。通过苏木精和伊红染色检测胰腺和胎盘损伤。结果表明，与正常妊娠大鼠相比，GDM 大鼠中 miR-875-5p 的表达水平下调，而 TXNRD1 的表达水平上调。miR-875-5p 可显著调节 GDM 大鼠中 TXNRD1 的表达。miR-875-5p 沉默可显著降低 FBG 和胰岛素抵抗，同时降低血脂和促炎标志物的表达水平，并降低氧化应激。然而，miR-875-5p 的作用可被 TXNRD1 沉默逆转。因此，本研究表明，miR-875-5p 通过靶向 TXNRD1 调节 GDM 大鼠的 IR 和炎症。miR-875-5p 和 TXNRD1 可能是治疗 GDM 的潜在靶点。
