Diabetic neuropathy (DNP) is a severe complication of diabetes mellitus. In this study, we examined the potential of hesperidin (HES) to attenuate DNP and the involvement of the TRPM2 channel in this process. The rats were given a single dose of 45 mg/kg of streptozotocin (STZ) intraperitoneally to induce diabetic neuropathic pain. On the third day, we confirmed the development of diabetes in the DNP and DNP + HES groups. The HES groups were treated with 100 mg/kg and intragastric gavage daily for 14 days. The results showed that treatment with HES in diabetic rats decreased STZ-induced hyperglycemia and thermal hyperalgesia. Furthermore, in the histopathological examination of the sciatic nerve, HES treatment reduced STZ-induced damage. The immunohistochemical analysis also determined that STZ-induced increased TRPM2 channel, type-4 collagen, and fibrinogen immunoactivity decreased with HES treatment. In addition, we investigated the TRPM2 channel activation in the sciatic nerve damage mechanism of DNP model rats created by STZ application using the ELISA method. We determined the regulatory effect of HES on increased ROS, and PARP1 and TRPM2 channel activation in the sciatic nerves of DNP model rats. These findings indicated that hesperidin treatment could attenuate diabetes-induced DNP by reducing TRPM2 channel activation.

糖尿病神经病变（DNP）是糖尿病的严重并发症。在这项研究中，我们研究了橙皮苷 (HES) 减弱 DNP 的潜力以及 TRPM2 通道在此过程中的参与。给大鼠腹腔内单剂量45 mg/kg的链脲佐菌素(STZ)以诱导糖尿病神经性疼痛。第三天，我们确认DNP组和DNP+HES组患了糖尿病。HES组每天给予100mg/kg灌胃，连续14天。结果表明，糖尿病大鼠接受 HES 治疗可降低 STZ 诱导的高血糖和热痛觉过敏。此外，在坐骨神经的组织病理学检查中，HES 治疗减少了 STZ 引起的损伤。免疫组织化学分析还确定，STZ 诱导的 TRPM2 通道增加、4 型胶原和纤维蛋白原免疫活性随着 HES 治疗而降低。此外，我们采用ELISA方法研究了应用STZ建立的DNP模型大鼠坐骨神经损伤机制中TRPM2通道激活的情况。我们确定了 HES 对 DNP 模型大鼠坐骨神经中 ROS 增加以及 PARP1 和 TRPM2 通道激活的调节作用。这些发现表明，橙皮苷治疗可以通过减少 TRPM2 通道激活来减弱糖尿病诱导的 DNP。