The present study was designed to investigate the roles of P2X3 receptors in dorsal root ganglion (DRG) neurons in colonic hypersensitivity and the effects of alpha-lipoic acid (ALA) on P2X3 receptor activity and colonic hypersensitivity of diabetic rats. Streptozotocin (STZ) was used to induce diabetic model. Abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) was recorded as colonic sensitivity. ATP-induced current density of colon-specific DRG (T13-L2 DRGs) neurons was measured with whole-cell patch clamp. The expression of P2X3Rs of T13-L2 DRGs was measured by western blot analysis. The results showed that AWR scores significantly increased after STZ injection. P2X3R expression and ATP current density of T13-L2 DRG neurons were enhanced in diabetic rats. Intraperitoneal injection with ALA once a day for 1 week remarkably reduced P2X3R expression and ATP current density in diabetic rats. Importantly, ALA treatment attenuated colonic hypersensitivity in diabetic rats. Our data suggest that STZ injection increases expression and function of P2X3 receptors of colon-specific DRG neurons, thus contributing to colonic hypersensitivity in diabetic rats. Administration of ALA attenuates diabetic colonic hypersensitivity, which is most likely mediated by suppressing expression and function of P2X3 receptors in DRGs of diabetic rats.

译文

本研究旨在研究背根神经节 (DRG) 神经元中P2X3受体在结肠超敏反应中的作用以及 α-硫辛酸 (ALA) 对糖尿病大鼠P2X3受体活性和结肠超敏反应的影响。链脲佐菌素 (STZ) 用于诱导糖尿病模型。对结直肠扩张 (CRD) 反应的腹部撤药反射 (AWR) 被记录为结肠敏感性。用全细胞膜片钳测量ATP诱导的结肠特异性DRG (T13-L2 DRGs) 神经元的电流密度。通过蛋白质印迹分析测量T13-L2 DRGs中P2X3Rs的表达。结果显示,注射STZ后AWR评分明显升高。糖尿病大鼠T13-L2 DRG神经元P2X3R表达和ATP电流密度增强。每天一次腹腔注射ALA,持续1周,可显着降低糖尿病大鼠的P2X3R表达和ATP电流密度。重要的是,ALA治疗可减轻糖尿病大鼠的结肠超敏反应。我们的数据表明,STZ注射可增加结肠特异性DRG神经元的P2X3受体的表达和功能,从而导致糖尿病大鼠的结肠超敏反应。ALA的给药可减轻糖尿病结肠超敏反应,这很可能是通过抑制糖尿病大鼠DRGs中P2X3受体的表达和功能来介导的。

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