Huang Lan-Ji, Jia Shu-Shan, Sun Xue-Hua, Li Xin-You, Wang Fei-Fei, Li Wei, Jin Qing-Song
Department of Anesthesiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China.
Department of Endocrinology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China.
Exp Ther Med. 2020 Sep;20(3):2684-2690. doi: 10.3892/etm.2020.9019. Epub 2020 Jul 17.
In the present study, the ability of baicalin to relieve neuropathic pain due to spinal nerve ligation in rats was explored, and the relationship between baicalin and α-adrenoceptors (α-AR) was determined. The neuropathic pain model was established by ligating the L5-L6 spinal nerves in Sprague-Dawley rats. Several α-AR antagonists were injected into the intramedullary sheath to evaluate the role of baicalin in neuropathic pain. The antagonists included nonselective α-AR antagonist idazoxan, α-AR antagonist BRL 44408, α-AR antagonist ARC 239 and α-AR antagonist JP 1302. The rats were divided into an untreated control group, saline group, baicalin group and baicalin + α-AR antagonist groups. Paw withdrawal threshold (PWT) was tested to assess the level of pain felt by the rats. The levels of α-AR mRNA were tested by reverse transcription-quantitative PCR. Inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17 and IL-1β, were analyzed by ELISA. The histopathological changes were assessed by hematoxylin and eosin staining. Flow cytometry was used to examine the percentage of CD4 peripheral blood mononuclear cells (PBMCs). Compared with the saline group, the PWT value increased after treating with baicalin. However, intrathecal injection of α-AR antagonist reversed the antinociceptive effects of baicalin. Compared with the saline group, the expression of α-AR and α-AR mRNA was upregulated significantly in the baicalin group (P<0.05). Levels of α-AR mRNA were also decreased in the baicalin + idazoxan group compared with the baicalin group (P<0.05). The levels of TNF-α, IL-6, IL-17 and IL-1β were raised after treatment with baicalin. In addition, baicalin treatment ameliorated the histological damage in the spinal cord. The percentage of CD4 PBMCs was increased in the saline group compared with the control group (P<0.05). Compared with the baicalin group, the percentage of CD4+ PBMCs was raised after treatment with the α-AR antagonists. In conclusion, intrathecal injection of baicalin produced an antiallodynic effect in a spinal nerve ligation-induced neuropathic pain model. The mechanism may be related to the regulation of a-AR expression.
在本研究中，探讨了黄芩苷缓解大鼠脊髓神经结扎所致神经性疼痛的能力，并确定了黄芩苷与α-肾上腺素能受体（α-AR）之间的关系。通过结扎Sprague-Dawley大鼠的L5-L6脊髓神经建立神经性疼痛模型。将几种α-AR拮抗剂注入髓鞘内以评估黄芩苷在神经性疼痛中的作用。拮抗剂包括非选择性α-AR拮抗剂咪唑克生、α-AR拮抗剂BRL 44408、α-AR拮抗剂ARC 239和α-AR拮抗剂JP 1302。将大鼠分为未治疗对照组、生理盐水组、黄芩苷组和黄芩苷+α-AR拮抗剂组。测试爪部退缩阈值（PWT）以评估大鼠的疼痛程度。通过逆转录定量PCR检测α-AR mRNA的水平。采用酶联免疫吸附测定法分析包括肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-17和IL-1β在内的炎症因子。通过苏木精和伊红染色评估组织病理学变化。采用流式细胞术检测CD4外周血单个核细胞（PBMC）的百分比。与生理盐水组相比，黄芩苷治疗后PWT值升高。然而，鞘内注射α-AR拮抗剂可逆转黄芩苷的抗伤害感受作用。与生理盐水组相比，黄芩苷组α-AR和α-AR mRNA的表达显著上调（P<0.05）。与黄芩苷组相比，黄芩苷+咪唑克生组α-AR mRNA的水平也降低（P<0.05）。黄芩苷治疗后TNF-α、IL-6、IL-17和IL-1β的水平升高。此外，黄芩苷治疗改善了脊髓的组织学损伤。与对照组相比，生理盐水组CD4 PBMCs百分比增加（P<0.05）。与黄芩苷组相比，α-AR拮抗剂治疗后CD4+ PBMCs百分比升高。总之，鞘内注射黄芩苷在脊髓神经结扎诱导的神经性疼痛模型中产生抗痛觉过敏作用。其机制可能与α-AR表达的调节有关。
