RESUMO
Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression.
Assuntos
Astrócitos , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , MicroRNAs , Septinas , Animais , Masculino , Camundongos , Astrócitos/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/etiologia , Modelos Animais de Doenças , MicroRNAs/genética , MicroRNAs/metabolismo , Neuralgia/metabolismo , Neuralgia/genética , Neuralgia/etiologia , Septinas/genética , Septinas/metabolismoRESUMO
Although some investigations have been performed to determine the effects of transfusion load and suction pressure on renal function during intraoperative salvage autotransfusion, the precise threshold is still undetermined. A total of 625 patients undergoing surgery with the Continuous AutoTransfusion System (CATSplus) were enrolled and divided into groups according to the utilized suction pressure and transfusion volume. Plasma free hemoglobin (FHB) and creatinine clearance (CCr) were assayed to indicate the renal function. Both 0.03 MPa suction (≥4-unit load) and >5 units transfusion changed the levels of FHB and CCr significantly when measured 24 h post-operation compared to pre-operation. Under 0.02 MPa suction (≥4-unit load), the alteration of FHB and CCr returned to normal after 24 h. Under 3 units transfusion, the levels of FHB and CCr at 6 and 12 h post-operation changed significantly compared to pre-operation (P<0.05 or P<0.01, respectively), and this alteration could be restored to normal at 72 h post-operation. After an exhaustive investigation, less than 4 units transfusion and less than 0.03 MPa suction pressure are recommended for intraoperative salvage autotransfusion.