Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215008, People's Republic of China.
Drug Des Devel Ther. 2023 Jul 28;17:2239-2257. doi: 10.2147/DDDT.S415127. eCollection 2023.
The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism.
The potential mechanism of ZQGCD's therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software.
Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream.
The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression.
本研究旨在探讨枳芪甘草汤（ZQGCD）对腰椎间盘突出症（LDH）痛觉过敏的影响及其机制。
采用网络药理学筛选入血的 8 种成分的作用靶点，探讨 ZQGCD 治疗 LDH 的潜在机制。体外研究 CCR2 抑制剂和含 ZQGCD 血清对 CCL2/CCR2 信号通路和背根神经节神经元（DRGn）兴奋性的影响。体内研究 CCR2 抑制剂和 ZQGCD 对大鼠椎间盘和背根神经节（DRG）中 CCL2/CCR2 信号通路和 ASIC3 表达、LDH 大鼠椎间盘退变程度、足退缩阈值和足退缩潜伏期的影响。采用 AutodockVina 1.2.2 软件分析 CCR2 与入血成分的结合亲和力和相互作用模式。
网络药理学表明，ZQGCD 可通过趋化因子信号通路治疗 LDH。结果发现，CCR2 抑制剂和含 ZQGCD 血清可下调 CCR2 和 ASIC3 的表达，降低 DRGn 细胞的兴奋性。CCL2/CCR2 信号通路在 LDH 大鼠退变椎间盘和 DRG 中被激活，增加了 ASIC3 的表达，降低了机械性痛觉过敏和热痛觉过敏域。然而，CCR2 抑制剂或 ZQGCD 可改善 LDH 大鼠的上述变化。靶蛋白 CCL2 和 CCR2 与入血的 8 种成分具有很强的亲和力。
CCL2/CCR2 通路在 LDH 大鼠椎间盘和 DRG 中被激活，同时伴随着 ASIC3 表达上调、DRGn 兴奋性增加和痛觉过敏的发生。ZQGCD 通过抑制 CCL2/CCR2 通路和下调 ASIC3 表达来改善 LDH 大鼠的痛觉过敏。
