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目的研究安络小皮伞醇提取物(MAEE)对坐骨神经慢性压迫性损伤(CCI)所致神经病理性疼痛大鼠的镇痛作用并探索其作用机制。方法 40只成年SD大鼠随机分为假手术组、模型组及MAEE高、中、低剂量(800、400、200 mg/kg)组,每组8只。CCI术后14 d,连续ig给药7 d。于1、3、5、7 d给药后2 h测定大鼠机械痛阈(MWT)值和热痛阈(TWL)值,并在停药后连续测定3 d。于给药7 d后,取各组大鼠脊髓L4-L6节段,ELISA及实时荧光定量PCR(q RT-PCR)法检测炎症因子肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β)的表达,Western blotting法检测MAPK家族蛋白p-ERK、p-p38、p-JNK的表达变化。结果与模型组比较,连续7 d给予MAEE能够剂量依赖性的缓解CCI诱导的大鼠机械学过敏及热痛学超敏(P<0.05、0.01);下调CCI大鼠脊髓L4-L6节段炎症因子TNF-α和IL-1β的水平以及p-ERK、p-p38、p-JNK的蛋白表达(P<0.05、0.01)。结论 MAEE剂量依赖性的缓解CCI诱导的机械学超敏及热痛学过敏,该作用可能与其抑制CCI大鼠脊髓TNF-α、IL-1β等炎性细胞因子的表达及降低MAPK磷酸化蛋白表达相关。
Objective To study the analgesic effect of MAEE on neuropathic pain induced by chronic constriction injury (CCI) in sciatic nerve and to explore its mechanism. Methods 40 adult SD rats were randomly divided into sham operation group, model group and high, medium and low doses of MAEE (800, 400, 200 mg / kg) group, with 8 in each group. 14 days after CCI, continuous ig administration for 7 days. The mechanical pain threshold (MWT) and thermal pain threshold (TWL) were measured at 1, 3, 5 and 7 days after administration, and were measured continuously for 3 days after discontinuation. At 7 days after administration, L4-L6 segments of spinal cord of each group were taken and the levels of TNF-α and IL-6 were detected by ELISA and qRT-PCR. 1β (IL-1β) were detected by Western blotting. The expressions of p-ERK, p-p38 and p-JNK were detected by Western blotting. Results Compared with the model group, administration of MAEE for 7 days continuously reduced CCI-induced mechanical and thermal hyperalgesia (P <0.05, 0.01) and down-regulated the L4-L6 segment inflammation in the spinal cord of CCI rats The levels of TNF-α and IL-1β and the protein expressions of p-ERK, p-p38 and p-JNK (P <0.05, 0.01). Conclusion MAEE can relieve CCI-induced mechanical hyperalgesia and thermo-pain sensitization in a dose-dependent manner, which may be related to its inhibitory effect on the expression of inflammatory cytokines such as TNF-α and IL-1β in spinal cord of rats with CCI and the decrease of MAPK phosphorylation protein expression Related.