六味地黄汤及“补泻”药对对肾阴虚模型小鼠下丘脑-垂体-性腺轴功能的影响

Effects of Liuwei Dihuang Decoction and “Reinforcing and Reducing” Herb Couples on HPG Axis in Kidney Yin Deficiency Mice

目的观察六味地黄汤及其3个"一补一泻"药对对肾阴虚模型小鼠下丘脑-垂体-性腺(HPG)轴功能及性腺组织形态的影响。方法将60只小鼠随机分为空白对照组、模型组、六味地黄汤组、山茱萸-牡丹皮组、熟地黄-泽泻组、山药-茯苓组共6个试验组;连续9 d分别灌胃给予以上对应药物;第5~9天,除空白对照组灌胃蒸馏水外,其他各组按50 mg·kg?1体质量每天灌胃氢化可的松注射液建立模型,用ELISA法检测血浆环磷酸腺苷(c AMP)、环磷酸鸟苷(c GMP)含量,用放射免疫分析法检测促卵泡素(FSH)、雌二醇(E2)及睾酮(T)含量,并用HE染色法观察性腺(睾丸、子宫)病理切片。结果与空白对照组比较,肾阴虚模型小鼠血浆c AMP含量升高,血浆c GMP及血清FSH、E2、T含量降低,有显著性差异(P<0.01),性腺组织受损;与模型组比较,六味地黄汤组及山茱萸-牡丹皮药对组均能上调肾阴虚小鼠血浆c GMP及血清FSH、E2、T含量,下调血浆c AMP含量,有显著性差异(P<0.05,P<0.01),修复性腺组织,其中山茱萸-牡丹皮药对药效略低于六味地黄汤,而熟地-泽泻药对及山药-茯苓药对对肾阴虚小鼠基本无影响。结论六味地黄汤能改善肾阴虚证,并对其引起的HPG轴功能紊乱有调节作用,其中仅山茱萸-牡丹皮药对的作用更近似于全方,可能是全方改善肾阴虚证的主要药效组成部分;说明3个"一补一泻"药对的协同作用是六味地黄汤调节HPG轴功能的重要基础,从而产生了六味地黄汤的综合作用,体现了其全方配伍高度的科学内涵。

OBJECTIVE To observe the effect of Liuwei Dihuang Decoction and three ＂reinforeing and reducing＂ herb couples on hypothalamus-pituitary-gonad（HPG） axis and morphologic changes of the gonad in kidney Yin deficiency mice. METHODS The mice were randomly divided into six experimental groups： blank group, model group, Liuwei Dihuang decoction group, Corni Fructus-Moutan Cortex couple group, Rehmanniae Radix Praeparata couple group and Dioscoreae Rhizoma-Poria couple group. The rats were gavaged with oral administration of corresponding medicines for 9 days. On 5？9 d, in addition to the blank group were given distilled water, the other groups were gavaged with hydrocortisone injection per day according to 50 mg·kg？1 body weight. The contents of cyclic adenosine monophosphate（c AMP）, cyclic guanosine monophosphate（c GMP） and follicle-stimulating hormone（FSH）, estradiol（E2）, testosterone（T） were determined by ELISA and radio immunoassay, gonad was observed. RESULTS Compared with blank group, the plasma c AMP, serum FSH, E2, T contents were increased, while plasma c GMP in kidney Yin deficiency were decreased, the difference was statistically significant（P〈0.01）; gonad tissue damaged. Compared with model group, Liuwei Dihuang decoction and Corni Fructus-Moutan Cortex moutan couple group could increase plasma c GMP, serum FSH, E2, T contents and decrease the plasma c AMP contents（P〈0.05 or P〈0.01）, the damaged gonad tissue were repaired. CONCLUSION Liuwei Dihuang decoction could improve kidney Yin deficiency syndrome and regulate the dysfunction of HPG axis, while only Corni Fructus-Moutan Cortex couple is approximate to the whole function; it illustrated that the synergistic action of three ＂reinforeing and reducing＂ herb couples are the important basis of Liuwei Dihuang decoction to regulate the HPG axis, which reflects the scientific connotation of the compatibility of the whole herbs.