Cardiac autonomic neuropathy resulting from human immunodeficiency virus (HIV) infection is common; however, its mechanism remains unknown. The current work attempted to explore the function and mechanism of the P2Y₁₃ receptor in HIV-glycoprotein 120 (gp120)-induced neuropathy in cervical sympathetic ganglion. The superior cervical ganglion (SCG) of the male SD rat was coated with HIV-gp120 to establish a model of autonomic neuropathy. In each group, we measured heart rate, blood pressure, heart rate variability, sympathetic nerve discharge and cardiac function. The expression of P2Y₁₃ mRNA and protein in the SCG was tested by real-time polymerase chain reaction and western blotting. Additionally, this study focused on identifying the protein levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), Caspase-1, Gasdermin D (GSDMD), interleukin (IL)-1β and IL-18 in the SCG using western blotting and immunofluorescence. In gp120 rats, increased blood pressure, heart rate, cardiac sympathetic nerve activity, P2Y₁₃ receptor levels and decreased cardiac function could be found. P2Y₁₃ shRNA or MRS2211 inhibited the above mentioned changes induced by gp120, suggesting that the P2Y₁₃ receptor may be engaged in gp120-induced sympathetic nerve injury. Moreover, the levels of NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 in the gp120 group were increased, while significantly decreased by P2Y₁₃ shRNA or MRS2211. Therefore, the P2Y₁₃ receptor is involved in gp120-induced sympathetic neuropathy, and its molecular mechanism shows an association with the activation of the NLRP3 inflammasome, followed by GSDMD formation along with the release of inflammatory factors including IL-1β and IL-18.

由人类免疫缺陷病毒（HIV）感染引起的心脏自主神经病变很常见；然而，其机制仍不清楚。本研究试图探讨P2Y ₁₃受体在HIV糖蛋白120（gp120）诱导的颈交感神经节神经病变中的功能和机制。将HIV-gp120包被雄性SD大鼠的颈上神经节（ SCG） ，建立自主神经病变模型。在每组中，我们测量了心率、血压、心率变异性、交感神经放电和心脏功能。通过实时聚合酶链反应和蛋白质印迹法检测SCG中_{P2Y 13 mRNA和蛋白}的表达。此外，本研究重点利用蛋白质印迹法鉴定 SCG 中NOD 样受体家族 Pyrin 结构域 3 (NLRP3)、Caspase-1、Gasdermin D (GSDMD)、白细胞介素(IL)-1β 和 IL-18 的蛋白水平。印迹和免疫荧光。在gp120大鼠中，可以发现血压、心率、心脏交感神经活动、P2Y _{13受体水平升高和心功能下降。}P2Y ₁₃ shRNA或MRS2211抑制gp120诱导的上述变化，表明P2Y ₁₃受体可能参与gp120诱导的交感神经损伤。此外，gp120组中NLRP3、Caspase-1、GSDMD、IL-1β和IL-18的水平升高，而P2Y ₁₃ shRNA或MRS2211则显着降低。因此，P2Y ₁₃受体参与 gp120 诱导的交感神经病变，其分子机制显示与 NLRP3 炎症小体的激活、随后 GSDMD 的形成以及包括 IL-1β 和 IL-18 在内的炎症因子的释放有关。