Long non-coding RNA MSTRG.81401 short hairpin RNA relieves diabetic neuropathic pain and behaviors of depression by inhibiting P2X4 receptor expression in type 2 diabetic rats
Long non-coding RNA MSTRG.81401 short hairpin RNA relieves diabetic neuropathic pain and behaviors of depression by inhibiting P2X4 receptor expression in type 2 diabetic rats
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DOI：
10.1007/s11302-021-09828-0
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发表时间：
2022-01-13
影响因子：
3.5
通讯作者：
Gao，Yun
中科院分区：
文献类型：
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作者：
Sun，Mengyun;Zhang，Mingming;Gao，Yun
糖尿病神经性疼痛（DNP）患者经历巨大的身体和精神痛苦，这与其他精神障碍（包括重度抑郁症（MDD））共病。P2X4受体是嘌呤能受体之一，是DNP和MDD的重要介质。本研究旨在确定长链非编码RNA (lncRNA) MSTRG.81401在缓解2型糖尿病大鼠DNP和mdd样行为中的作用和机制。经MSTRG.81401短发夹RNA （shRNA）给药后，模型+ MSTRG。81401 shRNA组表现出机械戒断阈值、热戒断潜伏期、野外试验和蔗糖偏好试验增加；然而，在强迫游泳测试中，静止时间减少了。MSTRG.81401 shRNA可显著降低模型+ MSTRG海马和脊髓中P2X4受体、肿瘤坏死因子-α和白细胞介素-1β的表达。81401 shRNA组。同时，MSTRG.81401 shRNA可下调海马和脊髓中ERK1/2的磷酸化。由此可见，lncRNA MSTRG.81401 shRNA可以减轻2型糖尿病大鼠DNP和mdd样行为，并可能下调大鼠海马和脊髓中P2X4受体的表达。
Patients with diabetic neuropathic pain (DNP) experience immense physical and mental suffering, which is comorbid with other mental disorders, including major depressive disorder (MDD). P2X4 receptor, one of the purinergic receptors, is a significant mediator of DNP and MDD. The present study aimed to identify the roles and mechanisms of MSTRG.81401, a long non-coding RNA (lncRNA), in alleviating DNP and MDD-like behaviors in type 2 diabetic rats. After administration with MSTRG.81401 short hairpin RNA (shRNA), the model + MSTRG.81401 shRNA group demonstrated increased mechanical withdrawal threshold, thermal withdrawal latency, open-field test, and sucrose preference test; however, immobility time on the forced swimming test decreased. MSTRG.81401 shRNA administration significantly decreased the expression of the P2X4 receptor, tumor necrosis factor-α, and interleukin-1β in the hippocampus and spinal cord in the model + MSTRG.81401 shRNA group. Simultaneously, MSTRG.81401 shRNA administration downregulated phosphorylation of ERK1/2 in the hippocampus and spinal cord. Thus, lncRNA MSTRG.81401 shRNA can alleviate DNP and MDD-like behaviors in type 2 diabetic rats and may downregulate the expression of P2X4 receptors in the hippocampus and spinal cord of rats.