地黄丸类方对肾阳虚大鼠HPA轴的影响

Effect of Dihuang Wan Formula Series on Hypothalamic-Pituitary-Adrenal Axis of Kidney-yang Deficiency Rats

目的比较桂附、知柏、六味地黄丸方对肾阳虚大鼠治疗作用的异同以及对下丘脑-垂体-肾上腺轴(HPA)的影响。方法取SD大鼠80只,随机分为8组(每组10只):正常组,模型组,六味地黄丸高、低剂量组(4,1 g·kg-1),知柏地黄丸高、低剂量组(4,1 g·kg-1),桂附地黄丸高、低剂量组(4,1 g·kg-1),灌胃给药,连续21 d。采用氢化可的松注射液肌注14 d的方法,制备大鼠肾阳虚模型,观察3种地黄丸方对肾阳虚大鼠的一般状态、体质量、肛温、血浆cAMP、cGMP、CRH、ACTH、血清CORT含量以及血浆cAMP/cGMP水平的影响。结果建模后大鼠体质量、肛温均有显著的降低,血浆cAMP水平无显著性变化,cGMP水平则显著升高,c AMP/c GMP比值显著下降,血浆CRH、ACTH和血清CORT水平均较正常组显著下降(P<0.05,P<0.01)。给药后,3种地黄丸类方均可显著升高肾阳虚大鼠体质量(P<0.05,P<0.01);桂附地黄丸表现出显著的升高肛温作用(P<0.05),六味地黄丸虽在后期表现出一定升温作用,而知柏地黄丸则未表现出升高肛温的作用(P>0.05);桂附地黄丸可显著升高cAMP/cGMP比值和恢复大鼠HPA轴功能(P<0.05,P<0.01),六味、知柏地黄丸组均无显著性改变。结论 3种地黄丸类方对肾阳虚大鼠生存状态及神经内分泌网络的影响方面存在明显差异,桂附地黄丸可以明显改善肾阳虚大鼠HPA轴抑制的状态;六味地黄丸对于肾阳虚大鼠免疫功能表现出一定的改善作用,知柏地黄丸改善作用不明显。

Objective To compare the therapeutic effects of Guifu Dihuang Wan, Zhibai Dihuang Wan, Liuwei Dihuang Wan,the Dihuang Wan formula series on the kidney-yang deficiency rats. Methods A total of 80 SD rats were evenly randomized into 8 groups,namely normal group,model group,high- and low-dose Liuwei Dihuang Wan groups（in the dosage of 4,1 g·kg^-1respectively）,high- and low-dose Zhibai Dihuang Wan groups（in the dosage of4, 1 g·kg-1respectively）, and high- and low-dose Guifu Dihuang Wan groups（in the dosage of 4, 1 g·kg^-1respectively）. Kidney-yang deficiency rat model was established by using classic method of intramuscular injection of hydrocortisone for two weeks. The medication groups were given the corresponding drug for 21 days. The therapeutic effects of the three kinds of Dihuang Wan formula were compared by observing the changes of rat general behavioral activities,body mass,rectal temperature,the contents of plasma cAMP,cGMP,CRH and ACTH,serum CORT,and cAMP/cGMP ratio. Results After modeling, body weight, rectal temperature and c AMP/c GMP ratio were significantly decreased,the plasma cGMP level was significantly elevated,hypothalamic-pituitary-adrenal（HPA）axis function was inhibited, plasma CRH, ACTH and serum CORT were significantly reduced in the model group as compared with the normal group（P 0.05）,but the plasma cAMP remained unchanged. After administration,body weight was increased in the six medication groups（P 0.05）. Rectal temperature was increased in Guifu Dihuang Wan groups（P 0.05）,was increased in Liuwei Dihuang Wan groups at later period,but stayed unchanged in Zhibai Dihuang Wan groups（P 0.05）. Guifu Dihuang Wan showed obvious effect on increasing cAMP/cGMP ratio and recovering HPA axis function（P 0.05）,but Zhibai Dihuang Wan and Liuwei Dihuang Wan had no effect on cAMP/cGMP ratio and HPA axis function. Conclusion Obvious differences exist in the effects of Guifu Dihuang Wan,Zhibai Dihuang Wan, and Liuwei Dihuang Wan on the survival state and neuroendocrine immune network of kidney-yang deficiency rats. Guifu Dihuang Wan can obviously improve HPA axis suppression,Liuwei Dihuang Wan can improve the immune function in kidney-yang deficiency rats,but the effect of Zhibai Dihuang Wan is weak.