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[摘要]
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(qRT-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。
[Key word]
[Abstract]
Objective To evaluate the analgesic effects and mechanism of Marasmius androsaceus ethanolic extract (MAEE) in chronic constriction injury induced neuropathic pain. Methods Totally 40 adult SD rats were randomly divided into Sham group, model group, high-, mid-, and low-dose (800, 400, and 200 mg/kg) MA groups. After 14 d of CCI, rats were continually treated with different doses of MAEE by ig administration for 7 d. Mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) were tested. After 7 d, spinal dorsal horns (L4-L6) of rats were taken. Expression of TNF-α and IL-1β was determined by ELISA and qRT-PCR respectively, and the expression level of MAPK signaling way proteins was determined by Western blotting in the spinal dorsal horn (L4-L6) of rats. Results Compared with model group, the pain threshold increased in MA group in a dose-dependent manner by repeated administration of MA for 7 d (P<0.05?0.01). The expression of TNF-α and IL-1β decreased after MA treated, and MA can also reduce the expression of p-ERK, p-p38, and p-JNK MAPK in spinal cord of CCI rats (P<0.05, 0.01). Conclusion MA can relieve the pain in rat models of chronic constriction injury of sciatic nerve in a dose-dependent manner. The possible mechanism is that attenuating the expression of TNF-α and IL-1β and decreasing the expression level of MAPK signaling way proteins in spinal cord.
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[基金项目]
江苏高校优势学科建设工程资助项目(PAPD)