中国药房2025，Vol.36Issue(10)：1191-1196,6.DOI:10.6039/j.issn.1001-0408.2025.10.07
安石榴苷对神经病理性疼痛大鼠的镇痛作用及机制
Analgesic effect and mechanism of punicalagin on neuropathic pain in rats
摘要
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 NLRP3 inflammasome in spinal dorsal horn microglia.关键词
安石榴苷/神经病理性疼痛/炎症/HIF-1α/NLRP3信号通路/脊髓背角Key words
punicalagin/neuropathic pain/inflammation/HIF-1α/NLRP3 signaling pathway/spinal dorsal horn分类
药学引用本文复制引用
汪莉,周伶,吴成龙..安石榴苷对神经病理性疼痛大鼠的镇痛作用及机制[J].中国药房,2025,36(10):1191-1196,6.基金项目
武汉市医学科研项目(No.WX18Q04) （No.WX18Q04）
