Department of Physiology, Basic Medical College, Nanchang University, Nanchang, Jiangxi 330006, PR China.
Affiliated Stomatological Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.
Brain Res Bull. 2018 May;139:56-66. doi: 10.1016/j.brainresbull.2018.02.005. Epub 2018 Feb 7.
Diabetic neuropathic pain (DNP) is one of the common complications of diabetes. Depression (DP) is also one of the common complications of diabetes. P2X receptors play an important role in the transmission of nociceptive signal and are associated with depressive illness. In the study, the hyperalgesia, allodynia and depressive behaviours of rats with comorbidity of DNP and DP were confirmed by the thermal withdrawal latency (TWL) test, mechanical withdrawal threshold (MWT) test, sucrose preference test (SPT), immobility time of forced swimming test (IMFST) and open-field test (OFT). The change in expression of the P2X receptor of the hippocampus was observed through RT-PCR, qPCR, Western blotting and immunohistochemical staining methods The results showed that palmatine treatment can alleviate the hyperalgesia, allodynia and depressive behaviours of rats with comorbidity of DNP and DP. Meanwhile, the expression of P2X receptors, GFAP, TNF-α and IL-1β in the hippocampus of the rats with comorbidity of DNP and DP was significantly increased compared with the control rats, and palmatine treatment could decrease the expression. Furthermore, the enhanced phosphorylation of ERK1/2 in the hippocampus of rats with DNP and DP was decreased noticeably by palmatine treatment. The results of this study suggest that palmatine can alleviate the comorbidity of DNP and DP by inhibiting the expression of P2X receptors in the hippocampus, and its action may be related to suppression of the phosphorylation of ERK1/2 and the release of TNF-α and IL-1β in the hippocampus.
糖尿病性神经病理性疼痛(DNP)是糖尿病的常见并发症之一。抑郁症(DP)也是糖尿病的常见并发症之一。P2X 受体在伤害性信号的传递中发挥重要作用,与抑郁疾病有关。在研究中,通过热撤退潜伏期(TWL)试验、机械撤退阈值(MWT)试验、蔗糖偏好试验(SPT)、强迫游泳试验(IMFST)和旷场试验(OFT)证实了 DNP 和 DP 合并症大鼠的痛觉过敏、感觉异常和抑郁行为。通过 RT-PCR、qPCR、Western 印迹和免疫组织化学染色方法观察海马体 P2X 受体表达的变化。结果表明,小檗碱治疗可减轻 DNP 和 DP 合并症大鼠的痛觉过敏、感觉异常和抑郁行为。同时,与对照组大鼠相比,DNP 和 DP 合并症大鼠海马体中 P2X 受体、GFAP、TNF-α和 IL-1β的表达明显增加,小檗碱治疗可降低其表达。此外,小檗碱治疗可明显降低 DNP 和 DP 大鼠海马体中 ERK1/2 的磷酸化增强。本研究结果提示,小檗碱通过抑制海马体 P2X 受体的表达,可减轻 DNP 和 DP 的合并症,其作用可能与抑制海马体中 ERK1/2 的磷酸化及 TNF-α和 IL-1β的释放有关。