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制川乌与白芍组分配伍治疗类风湿性关节炎的作用机理研究

The Empirical Study on Mechanism of Action of Curing Rheumatoid Arthritis with the Compatibility Composition about Radix Aconiti Preparata and Raidix Paeoniae Alba

【作者】 李晋奇

【导师】 彭成;

【作者基本信息】 成都中医药大学 , 方剂学, 2008, 博士

【摘要】 目的:从制川乌与白芍组分配伍层面上研究其抗炎、镇痛、解毒、以及治疗类风湿性关节炎的作用,确定其增效的最佳配伍组分和最佳配伍比例,探讨制川乌与白芍组分配伍治疗类风湿性关节炎的作用机理。方法:从制川乌与白芍配伍水煎液和组分配伍两个层面,采用热板致痛试验、乙酸扭体致痛试验、二甲苯耳廓肿胀试验、蛋清足肿胀试验、风寒湿证类风湿性关节炎模型,研究其抗炎、镇痛以及治疗类风湿性关节炎的作用,同时采用急性毒性实验研究其组分配伍的解毒作用,确定其配伍增效、解毒以及治疗类风湿性关节炎的最佳配伍组分和最佳配伍比例。通过观察风寒湿证类风湿性关节炎下丘脑EOP(L-ENK、β-END)、血浆SP、血清细胞因子(1L-1β、TNF-α、IL-6、IL-2、IL-10)、血清IgG、滑膜细胞的超微结构等指标,探讨制川乌与白芍配伍组分配伍治疗类风湿性关节炎的作用机理。结果:1、制川乌与白芍配伍水煎液有明显提高热板致痛小鼠痛阈值、冰乙酸致痛小鼠痛阈值和抑制小鼠二甲苯耳廓肿胀的作用;制川乌与白芍配伍水煎液有明显提高风寒湿证类风湿性关节炎大鼠左、右关节痛阈的作用,有抑制风寒湿证类风湿性关节炎大鼠左、右关节肿胀,原发性和继发性关节病理改变的作用;并且大部分配伍比例效果优于单煎液,其中,制川乌与白芍1:2配伍水煎液效果最为明显。2、制川乌与白芍组分配伍有明显提高冰乙酸致痛小鼠痛阈值和热板致痛小鼠痛阈值的作用,有明显抑制小鼠二甲苯耳廓肿胀和大鼠蛋清足肿胀的作用:各组分中,制川乌总碱与白芍总苷、白芍多糖配伍的镇痛和抗炎作用较为明显;各配伍比例中,1:2配伍效果最为明显。制川乌总碱与白芍总苷、白芍多糖配伍有明显提高风寒湿证类风湿性关节炎大鼠左、右关节痛阈值的作用,有明显抑制风寒湿证类风湿性关节炎大鼠左、右关节肿胀、胸腺萎缩、脾脏肿大、原发性和继发性关节病理改变的作用;并且1:2配伍效果优于单组分。3、制川乌总碱与白芍总苷、白芍多糖不同比例配伍后LD50均较制川乌总碱的LD50明显增大;白芍总苷、白芍多糖可以降低制川乌总碱毒性。4、制川乌总碱与白芍总苷、白芍多糖配伍可以提高大鼠下丘脑的L-ENK和β-END的含量,降低血浆SP含量,升高血清IL-1β、IL-6含量,降低血清IL-2、IL-10含量;并且1:2配伍效果优于单组分。结论:制川乌与白芍配伍水煎液有明显镇痛、抗炎和治疗风寒湿证类风湿性关节炎的作用;其中,制川乌与白芍1:2配伍水煎液效果最明显。制川乌与白芍组分配伍有明显镇痛、抗炎和治疗风寒湿证类风湿性关节炎的作用;其中,制川乌总碱与白芍总苷或白芍多糖1:2配伍效果最明显。制川乌总碱与白芍总苷或白芍多糖配伍后毒性降低。制川乌总碱与白芍总苷或白芍多糖配伍治疗风寒湿证类风湿性关节炎的作用机理可能是增加中枢EOP的含量,抑制P物质合成和释放入血浆,调节血清细胞因子的紊乱,抑制血清免疫球蛋白的合成和分泌,减轻滑膜细胞异常亢进的分泌功能。

【Abstract】 Objective:To research the compatibility of composition about Radix Aconiti preparata and Raidix Paeoniae Alba on anti-inflammation effect,analgesia effect, deintoxication and curing rheumatoid arthritis.Find the best compatibility composition and proportion of synergistic effect.Explore the mechanism of action on compatibility composition curing rheumatoid arthritis.Methods:The pain test induced by hot-plate,the body-twisting test induced by acetic acid,the swelling test of the auricles induced by Xylene,the swelling degree test of feet induced by egg white and cold and dampness syndrome rheumatoid arthritis model of were used to research the compatibility effect of the water decoction and composition about Radix Aconiti preparata and Raidix Paeoniae Alba on anti-inflammation and analgesia and curing rheumatoid arthritis,and the acute toxicity test were used to research deintoxication.We found the best compatibility composition and proportion of synergistic effect,detoxication and curing rheumatoid arthritis.Finally,observed these indices such as endogenous opioid peptides(L-ENK,β-END) of hypothalamus,substance P,IgG of blood plasma,cell factors(IL-1β、TNF-a、IL-6、IL-2、IL-10) of blood plasma and the ultramicrostructure of synovial cell, we have explored the mechanism of action on compatibility composition curing rheumatoid arthritis.Results:1.The compatibility water decoction about Radix Aconiti preparata and Raidix Paeoniae Alba could elevate the pain threshold of mouse induced by hot-plate and acetic acid,and restrain the swelling of the mouse auricles induced by Xylene. The compatibility water decoction about Radix Aconiti preparata and Raidix Paeoniae Alba could elevate the pain threshold,and restrain the swelling and pathological changes of rats’ left or right articulus of rheumatoid arthritis of cold and dampness syndrome.The effect of most of the compatibility water decoction was better than single water decoction.The best compatibility proportion was 1:2.2.The compatibility composition about Radix Aconiti preparata and Raidix Paeoniae Alba could elevate the pain threshold of mouse induced by hot-plate and acetic acid,and restrain the swelling of the mouse auricles induced by Xylene or the rats feet induced by egg white.The compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony had better analgesia effect and anti-inflammation effect.The best compatibility proportion was 1:2.The compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony could elevate the pain threshold,and restrain the swelling,pathological changes of rats’ left or right articulus, Atrophy of thymus gland,tumidity of spleen of rheumatoid arthritis of cold and dampness syndrome.The effect of 1:2 was better than single composition.3.The LD50 of All compatibility proportion between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony became more than total base of Radix Aconiti preparata,therefore,total glucosides of paeony or polysaccharides of paeony could diminish the toxicity of total base of Radix Aconiti preparata.4.The compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony could elevate the contents of hypothalamic L-ENK andβ-END,degrade the contents of plasmatic SP,elevate the contents of serumal IL-1βand IL-6,degrade the contents of serumal IL-2 and IL-10.The effect of 1:2 was better than single composition.Conclusions:The compatibility water decoction about Radix Aconiti preparata and Raidix Paeoniae Alba had obviously the effect of analgesia,anti-inflammation,and curing rheumatoid arthritis.The best compatibility proportion was 1:2.The compatibility composition about Radix Aconiti preparata and Raidix Paeoniae Alba had obviously the effect of analgesia,anti-inflammation,and curing rheumatoid arthritis.The best compatibility compositions were between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony.The best compatibility proportion was 1:2.The toxicity of compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony decreased.The compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony could cure rheumatoid arthritis.The mechanism of action might be that the contents of center EOP had increased,the synthesis and release of SP had been restrained,the disturbance of serumal cell factor had been adjusted,the synthesis and secretion of serum immune globulin had been restrained,and the anomal-excitatory secretory action of synovial cell had been relieved.

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