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目的:观察不同剂量雷公藤内酯醇(triptolide,TP)对佐剂性关节炎(adjuvant arthritis,AA)大鼠的镇痛效应,及相应节段脊髓背角和背根神经节(dorsal root ganglion,DRG)中诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、P物质(substance P,SP)表达的影响,探讨TP对类风湿性关节炎(RA)镇痛作用的可能机制。方法:选用SD大鼠50只,随机分成正常组(A组)、模型组(B组)、TP低(C组)、中(D组)、高(E组)剂量治疗组。除A组外,每组大鼠右后足跖皮内注入0.1 mL弗氏完全佐剂造模。造模后14 d,C,D,E组大鼠采取不同剂量(C组0.1 mg·kg-1,D组0.2 mg·kg-1,E组0.4 mg·kg-1)TP腹腔注射给药,每天1次,连续给药9 d之后检测50%机械痛阈(mechanical withdraw threshold,MWT),用免疫组织化学方法检测腰5(L5)脊髓背角和DRG节段中iNOS,SP的表达变化情况。结果:B组大鼠50%MWT显著低于A组(P<0.01),经过TP治疗后,C,D,E组热痛阈显著高于B组(P<0.01),TP可显著提高AA大鼠MWT,呈一定的量效关系;免疫组化结果表明,B组iNOS,SP阳性表达水平显著升高(P<0.01),而C,D,E组大鼠L5节段脊髓背角和DRG中iNOS,SP阳性表达水平显著低于B组(P<0.01),呈一定的量效关系。结论:TP对AA具有良好镇痛作用;TP可抑制AA大鼠脊髓背角和DRG中iNOS,SP的表达,这可能是TP产生镇痛作用机制之一。
OBJECTIVE: To observe the analgesic effects of different doses of triptolide (TP) on adjuvant arthritis (AA) in rats and the corresponding dorsal root ganglion (DRG) DRG) on expression of inducible nitric oxide synthase (iNOS) and substance P (SP) in rats with rheumatoid arthritis (RA). Methods: Fifty SD rats were randomly divided into normal group (A group), model group (B group), TP low group (C group), medium (D group) and high (E group) dose treatment group. Except for group A, each rat was injected intradermally with 0.1 mL Freund’s complete adjuvant intradermally. At 14 days after model establishment, C, D and E groups were given intraperitoneal injection of TP (0.1 mg · kg-1 in group C, 0.2 mg · kg-1 in group D and 0.4 mg · kg-1 in group E) , Once daily and 50% mechanical withdrawal threshold (MWT) after continuous administration for 9 days. The expressions of iNOS and SP in spinal dorsal horn and DRG segment of lumbar 5 (L5) were detected by immunohistochemistry Happening. Results: The 50% MWT in group B was significantly lower than that in group A (P <0.01). After TP treatment, the pain thresholds in groups C, D and E were significantly higher than those in group B (P <0.01) The MWT of rats showed a dose-response relationship. The results of immunohistochemistry showed that the positive expression of iNOS and SP in group B was significantly increased (P <0.01), while the dorsal angle of L5 spinal cord in group C, D and E The expression of iNOS and SP in DRG was significantly lower than that in group B (P <0.01), showing a dose-response relationship. CONCLUSION: TP has a good analgesic effect on AA. TP inhibits the expression of iNOS and SP in spinal dorsal horn and DRG of AA rats, which may be one of the mechanisms of TP analgesia.