穿心莲内酯对大鼠神经性疼痛的影响机制
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篇名: 穿心莲内酯对大鼠神经性疼痛的影响机制
TITLE: Effect mechanism of andrographolide on neuropathic pain in rats
摘要: 目的 研究穿心莲内酯对大鼠神经性疼痛(NP)的影响机制。方法将大鼠随机分为假手术组、模型组、穿心莲内酯低剂量组(1mg/kg)、穿心莲内酯中剂量组(5mg/kg)、穿心莲内酯高剂量组(10mg/kg)、阿魏酸钠组(150mg/kg),每组12只。除假手术组外,其余各组大鼠均采用坐骨神经慢性压迫损伤法复制NP模型。建模成功后,各给药组大鼠鞘内注射相应剂量的穿心莲内酯或灌胃相应剂量的阿魏酸钠,假手术组和模型组大鼠给予等体积生理盐水,每日1次,连续14d。给药7、14d时检测各组大鼠的机械性缩足反射阈值(MWT)和热刺激缩足反射潜伏期(TWL);末次给药后,检测各组大鼠血清中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、前列腺素E(2PGE2)、P物质(SP)水平,观察脊髓组织病理形态,检测脊髓组织中离子钙接头蛋白分子1(Iba-1)、生长停滞特异性蛋白6(Gas6)、受体型酪氨酸激酶Axl(简称“Axl”)mRNA及蛋白表达量。结果与模型组比较,各给药组大鼠给药7、14d时MWT、TWL以及末次给药后Gas6、AxlmRNA及蛋白表达量均显著升高(P<0.05),IL-6、TNF-α、PGE2、SP水平和Iba-1mRNA及蛋白表达量均显著降低(P<0.05),脊髓组织神经元排列紊乱、毛细血管扩张充血等病理损伤均不同程度减轻;穿心莲内酯高剂量组与阿魏酸钠组大鼠上述指标比较,差异均无统计学意义(P>0.05)。结论穿心莲内酯可能通过激活Gas6/Axl信号轴来抑制炎症反应,从而发挥缓解NP的作用。
ABSTRACT: OBJECTIVE To investigate the effect mechanism of andrographolide (Andro) on neuropathic pain (NP) in rats. METHODS Rats were randomly separated into sham operation group, model group, Andro low-dose (1 mg/kg), Andro medium-dose (5 mg/kg) and Andro high-dose (10 mg/kg) groups, and sodium ferulic acid (150 mg/kg) group, with 12 rats in each group. Except for sham operation group, other groups used the chronic sciatic nerve compression injury method to induce NP model. After modeling, each group was given relevant dose of Andro intrathecally or sodium ferulate intragastrically. The sham operation group and model group were given a constant volume of normal saline once a day for 14 consecutive days. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats were detected in each group after 7 and 14 days of administration. After the last medication, the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and substance P (SP) in rats were detected in each group, and the pathological morphology of spinal cord tissue was observed. mRNA and protein expressions of ionized calcium binding adaptor molecule-1 (Iba-1), growth arrest specific protein 6 (Gas6), and Axl in spinal cord tissue were determined. RESULTS Compared with model group, MWT and TWL after 7 and 14 days of the administration, the mRNA and protein expressions of Gas6 and Axl after the last medication were all increased significantly in administration groups (P<0.05), while the levels of IL-6, TNF-α, PGE2 and SP, mRNA and protein expressions of Iba-1 were all decreased significantly (P<0.05); pathological injuries such as the disordered arrangement of spinal cord neurons and dilation and congestion of capillaries had been alleviated to varying degrees. Compared with sodium ferulic acid group, there was no statistically significant difference in the above indicators in the Andro high-dose group (P>0.05). CONCLUSIONS Andro may inhibit inflammatory response by activating the Gas6/Axl signaling axis, thereby alleviating NP.
期刊: 2024年第35卷第20期
作者: 陈天华;江群;董航
AUTHORS: CHEN Tianhua,JIANG Qun,DONG Hang
关键字: 穿心莲内酯;神经性疼痛;Gas6/Axl信号轴;镇痛
KEYWORDS: andrographolide; neuropathic pain; Gas6/Axl signal axis; analgesia
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