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长链非编码 RNA UC.360+ shRNA 通过星状神经节 P2X4 受体改善糖尿病心脏自主神经功能障碍。

LncRNA UC.360+ shRNA Improves Diabetic Cardiac Sympathetic Dysfunction Mediated by the P2X4 Receptor in the Stellate Ganglion.

机构信息

Neuropharmacology Laboratory, Physiology Department, Basic Medical School of Nanchang University, Nanchang 330006, P. R. China.

Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi 330006, P. R. China.

出版信息

ACS Chem Neurosci. 2021 Apr 7;12(7):1210-1218. doi: 10.1021/acschemneuro.1c00050. Epub 2021 Mar 18.

Abstract

Diabetic cardiac autonomic neuropathy (DCAN) is a complication that affects more than 60% of diabetic patients. There is evidence for the involvement of P2X4 receptor in DCAN. This study showed that the expression of the long noncoding RNA (lncRNA) UC.360+ was increased in the stellate ganglion (SG) of type 2 diabetes mellitus (DM) rats, and hybridization revealed a clear presence of UC.360+ in SG neurons. The potential roles of UC.360+ in DCAN and its relationship with P2X4 receptor in SG were further explored via application of the short hairpin RNA (shRNA) against lncRNA UC.360+ in DM rats. The abnormal cardiac sympathetic changes in diabetic rats were improved after treatment with lncRNA UC.360+ shRNA. In the SG of these shRNA-treated DM rats, the upregulation of P2X4, tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and phosphorylated ERK1/2 was inhibited. Thus, lncRNA UC.360+ shRNA treatment may improve DCAN mediated by the P2X4 receptor in SG.

摘要

糖尿病心脏自主神经病变(DCAN)是一种影响超过 60%糖尿病患者的并发症。有证据表明 P2X4 受体参与了 DCAN。本研究表明,长链非编码 RNA(lncRNA)UC.360+在 2 型糖尿病(DM)大鼠的星状神经节(SG)中表达增加,杂交显示 UC.360+在 SG 神经元中清晰存在。通过在 DM 大鼠中应用针对 lncRNA UC.360+的短发夹 RNA(shRNA)进一步探讨了 UC.360+在 DCAN 中的潜在作用及其与 SG 中 P2X4 受体的关系。用 lncRNA UC.360+ shRNA 处理后,糖尿病大鼠的异常心脏交感神经变化得到改善。在这些 shRNA 处理的 DM 大鼠的 SG 中,P2X4、肿瘤坏死因子-α(TNF-α)、白细胞介素 1β(IL-1β)和磷酸化 ERK1/2 的上调受到抑制。因此,lncRNA UC.360+ shRNA 治疗可能通过 SG 中的 P2X4 受体改善 DCAN。

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