健脾化湿通络法对佐剂性关节炎大鼠HPA轴功能的影响

Effects of the Therapy of Invigorating spleen,Resolving Damp and Promoting Collaterals on HPA Axis Function in Adjuvant Arthritis Rats

目的观察佐剂性关节炎(adjuvant arthritis,AA)大鼠血清ACTH、CORT水平及下丘脑CRHmRNA、大脑皮质GRmRNA的表达,研究AA大鼠HPA轴的功能变化及中药干预机制。方法将84只Wistar雄性大鼠随机分为正常对照组、模型对照组、MTX组(甲氨蝶呤组)、TPT组(雷公藤多苷片组)、XFC低、中、高剂量组(新风胶囊低、中、高剂量组),每组12只。除正常对照组外,向每只大鼠右足跖皮内注射FCA0.1 mL致炎,复制佐剂性关节炎大鼠模型,致炎后第19天开始分组处理30d。采用ELISA法检测各组大鼠血清ACTH、CORT水平,RT-PCR法检测各组大鼠下丘脑CRHmR-NA、大脑皮质GRmRNA的表达。结果AA大鼠血清ACTH、CORT、大脑皮质GRmRNA表达显著升高(P<0.01),下丘脑中CRHmRNA表达显著降低(P<0.01);XFC治疗组能显著降低血清ACTH、CORT水平(P<0.01),下调大脑皮质GRmRNA表达(P<0.01),上调下丘脑CRHmRNA表达(P<0.01)。结论AA大鼠存在CRH分泌调节受损或下丘脑水平生物合成不足,健脾化湿通络方药通过降低血清ACTH及CORT水平,下调大脑皮质GRmRNA表达,上调下丘脑CRHmRNA表达,改善AA大鼠HPA轴功能紊乱,起到抗炎抗免疫的作用。

Objective To explore the changes of HPA axis function and the mechanism of traditional Chinese medicine intervention by observing the levels of serum ACTH and CORT as well as the expression of CRHmRNA in hypothalamus and GRmRNA in cerebral cortex in the rats with adjuvant arthritis（AA）.Methods 84 rats were randomly divided into normal control group,model control group,MTX group（methotrexate）,TPT group（tripterygium wilfordⅡ polycoride tablet）and low,middle and high dose groups of XFC（xinfeng capsule）,12 rats in each group.Except normal control group,FCA 0.1ml was injected intracutaneously on the right hindlimb of each rat to induce inflammation.AA rat model was duplicated.On the 19th day after inflammation induced,each group was managed for 30 days individually.ELISA method was used to determine the levels of ACTH and CORT in serum of each group.RT-PCR method was used to determine the expressions of CRHmRNA in hypothalamus and GRmRNA in cerebral cortex in AA rats.Results The levels of ACTH and CORT in serum and the expression of GRmRNA of cerebral cortex in AA rats increased markedly（P0.01）,and the expression of CRHmRNA in hypothalamus decreased markedly（P0.01）.XFC groups reduced the levels of ACTH and CORT in serum and degraded the expression of GRmRNA in cerebral cortex,and increased the expression of CRHmRNA in hypothalamus（P0.01）significantly.Conclusion AA rats have the damage of CRH secretion regulation or insufficient biosynthesis of hypothalamus.Chinese herbal medicines for invigorating the spleen,resolving damp and promoting collaterals can bring the action of anti-inflammation and anti-immunity into play through decreasing the levels of ACTH and CORT in serum,down-regulating the expression of GRmRNA in cerebral cortex,up-regulating the expression of hypothalamic CRHmRNA and improving in the disturbance of HPA axis function in AA rats.