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安石榴苷对神经病理性疼痛大鼠的镇痛作用及机制
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| 篇名： | 安石榴苷对神经病理性疼痛大鼠的镇痛作用及机制 |
| TITLE： | Analgesic effect and mechanism of punicalagin on neuropathic pain in rats |
| 摘要： | 目的 基于缺氧诱导因子1α（HIF-1α）/核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3（NLRP3）信号通路，探讨安石榴苷对神经病理性疼痛（NP）大鼠的镇痛作用及潜在机制。方法将雄性SD大鼠随机分为假手术组（18只）和造模组（72只），造模组大鼠以坐骨神经慢性压迫损伤法诱导建立NP模型。将造模成功的大鼠分为NP组、2-甲氧基雌二醇组（HIF-1α拮抗剂10mg/kg）、安石榴苷组（300mg/kg）、安石榴苷+二甲基草酰甘氨酸组（安石榴苷300mg/kg+HIF-1α激动剂175mg/kg），每组18只。各组大鼠腹腔注射和（或）灌胃相应药液或1%二甲基亚砜/生理盐水，每天1次，连续14d。末次给药后，检测各组大鼠的机械缩足反射阈值（MWT）、热缩足反射潜伏期（TWL）和脊髓组织中肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）、IL-6水平，观察其脊髓背角的形态学变化，检测其脊髓背角的神经元凋亡率、NLRP3/离子钙结合衔接分子1（Iba-1）共定位情况（以NLRP3+/Iba-1+细胞数计）以及脊髓组织中HIF-1α、NLRP3、凋亡相关斑点样蛋白（ASC）、胱天蛋白酶1（caspase-1）的表达情况。结果与假手术组比较，NP组大鼠脊髓背角中神经原纤维明显增粗并缠绕成结，可见含嗜银颗粒的空泡变性；其MWT、TWL均降低或缩短，脊髓组织中TNF-α、IL-1β、IL-6水平，脊髓背角神经元凋亡率，NLRP3+/Iba-1+细胞数以及HIF-1α、NLRP3、ASC、caspase-1蛋白的表达均显著升高或上调（P＜0.05）。与NP组比较，2-甲氧基雌二醇组和安石榴苷组大鼠上述指标均显著改善（P＜0.05），而二甲基草酰甘氨酸则可显著逆转安石榴苷对上述指标的改善作用（P＜0.05）。结论安石榴苷可缓解NP大鼠的疼痛，其镇痛作用可能是通过抑制HIF-1α/NLRP3信号通路、阻碍脊髓背角小胶质细胞中NLRP3炎症小体的活化来实现的。 |
| ABSTRACT： | OBJECTIVE To investigate the analgesic effect and potential mechanism of punicalagin on neuropathic pain （NP） rats based on the hypoxia-inducible factor-1α （HIF-1α）/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Male SD rats were randomly divided into sham operation group （18 rats） and modeling group （72 rats）. NP rat model was established by chronic constriction injury （CCI） of sciatic nerve. The successfully modeled rats were divided into NP group， 2-methoxyestradiol group （HIF-1α antagonist 10 mg/kg）， punicalagin group （300 mg/kg）， and punicalagin+dimethyloxaloglycine group （punicalagin 300 mg/kg+HIF-1α agonist 175 mg/kg）， with 18 rats in each group. Rats in each group were injected intraperitoneally and/or intragastrically with the corresponding solution or 1% dimethyl sulfoxide/normal saline， once a day， for 14 consecutive days. After the last administration， the mechanical withdrawal threshold （MWT）， thermal withdrawal latency （TWL）， the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-6 in spinal cord tissue were detected； the morphological changes in the spinal dorsal horn were observed. Apoptosis rate of spinal dorsal horn neurons， the co-localization of NLRP3/ionized calcium binding adapter molecule 1 （Iba-1） （calculated by the number of NLRP3+/Iba-1+ cells） and the protein expressions of HIF-1α， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC） and caspase-1 in spinal cord tissue were detected. RESULTS Compared with the sham operation group， neurofibril in spinal dorsal horn of rats in NP group was thickened and wound into knots， and vacuolar degeneration containing silver granules was observed； the MWT and TWL were reduced or shortened； the levels of TNF-α， IL-1β and IL-6 in spinal cord tissue， the apoptosis rate of spinal dorsal horn neurons， the number of NLRP3+/Iba-1+ cells， and protein expressions of HIF-1α， NLRP3， ASC and caspase-1 were significantly increased or up-regulated （P＜0.05）. Compared with the NP group， the above indexes were significantly improved in the 2-methoxyestradiol group and punicalagin group （P＜0.05）， while dimethyloxaloglycine could significantly reverse the improvement effect of punicalagin on the above indexes （P＜0.05）. CONCLUSIONS Punicalagin can relieve pain in NP rats， and its analgesic effect may be achieved by inhibiting HIF-1α/NLRP3 signaling pathway and blocking the activation of ma0o4e@163.com NLRP3 inflammasome in spinal dorsal horn microglia. |
| 期刊： | 2025年第36卷第10期 |
| 作者： | 汪莉；周伶；吴成龙 |
| AUTHORS： | WANG Li，ZHOU Ling，WU Chenglong |
| 关键字： | 安石榴苷；神经病理性疼痛；炎症；HIF-1α/NLRP3信号通路；脊髓背角 |
| KEYWORDS： | punicalagin； neuropathic pain； inflammation； |
| 阅读数： | 4 次 |
| 本月下载数： | 0 次 |
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