补肾方药对实验性骨质疏松症大鼠垂体-甲状腺轴及其骨密度的影响

背景将补肾方药分别制成"外贴剂"和"口服剂",根据"体表穴位-经络-内脏-靶器官"相关,分别用外贴穴位和口服两种不同的给药途径治疗骨质疏松,按照中医传统理论推测均会"归入肾经"而发挥调节作用,但实际上是否会有"靶向给药"的特异性?检测"下丘脑-垂体-靶腺"系统的激素,进一步分析肾、骨、子宫、甲状腺、睾丸等靶器官的雌激素受体和雄激素受体,观察"归经与受体"的相关性.设计以骨质疏松大鼠为研究对象的完全随机设计,补肾方药不同给药途径对照实验研究.目的探讨补肾方药对实验性骨质疏松垂体-甲状腺轴的影响.单位河北医科大学中医学院.材料实验于2000-01/2004-12在河北医科大学中西医结合基础实验室完成.选择3月龄健康SD雌性大鼠60只,体重(300±20)g.实验动物由河北省实验动物中心提供.大鼠在实验室常规喂养1周后,随机分成6组正常对照组(10只);病理模型组(10只);补肾方药总成分按0.8 g/100 g体质量灌喂组(10只);穴位贴剂外贴膀胱经穴位组(10只);穴位贴剂外贴肾经穴位组(10只);穴位贴剂外贴非经非穴位组(10只).方法采用注射地塞米松建立骨质疏松模型,用抗骨松穴位贴剂(antagonism osteoporosis acupoint paste,AOAP)外贴穴位、非经非穴位、并与口服补肾方药比较治疗骨质疏松(OP),以血清雌激素、骨密度、降钙素/甲状旁腺素、促甲状腺激素、游离T3、游离T4的变化为衡量指标,取垂体、甲状腺作促甲状腺激素细胞、C细胞和Tg等免疫细胞化学染色,并形态计量,观察其治疗效果.主要观察指标①补肾方药调节甲状腺功能;②补肾方药调节骨密度.结果AOAP能提高雌激素、降钙素/甲状旁腺素、促甲状腺激素、游离T3、游离T4的水平,增加骨密度;促甲状腺激素细胞、C细胞数目增多,Tg阳性反应物增多,颜色深.结论AOAP可以通过"多位点相关集合效应"综合调控影响骨代谢的内分泌功能,提高雌激素、降钙素/甲状旁腺素水平,扭转垂体-甲状腺轴功能减退的趋势,改善甲状腺的功能,使破骨细胞的骨吸收减弱,成骨细胞的骨形成增强,增加骨密度.

Effect of recipe for kidney tonification on pituitary-thyroid axis and bone density in rat with experimental osteoporosis

BACKGROUND: In the research, the recipe for kidney tonification is prepared into "topical form" and "oral form". According to the interrelationship of "acupoints-meridans and collaterals-internal organs-target organs", osteoporosis is treated by the approaches of point compress and oral application respectively. According to the traditional theory of Chinese medicine, it is to infer that the herbs bring the adjustment into play by "being attributive to kidney meridian", but,whether does the specialty of herbs on "targeting medication" happen practically or not? Hormones in "hypothalamus-pituitary- target gland" system is assayed to further analyze estrogen receptor and androgen receptor of target organs, such as kidney,bone, uterus, thyroid gland and testis so as to observe the relativity between "tropism and receptor".DESIGN: Complete random design with the objects of osteoporosis rats, and the control experimental study with kidney tonification recipe administrate with different approaches.OBJECTIVE: To probe into the effect of kidney tonification recipe on pituitary-thyroid axis in experimental osteoporosis.SETTING: College of Traditional Chinese Medicine of Hebei Medical University.MATERIALS: The experiment was performed in Chinese-Western integrated Basic Experiment Room of Hebei Medical University from January 2000 to December 2004. Sixty SD healthy female rats of 3-month old were employed,weighted (300 ± 20) g. The experimental animals were provided by Hebei Experimental Animal Center. After bred routinely for 1 week in Experimental Room, the rats were randomized into 6 groups, namely normal control(10rats), pathological model group(10 rats), infusing group(10 rats) in which kidney tonification recipe was applied based on 0. 8 g/100 g body mass,acupoint paste on bladder meridian group (10 rats), acupoint paste on kidney meridian group(10 rats) and paste on non-meridian group(10 rats). METHODS: Osteoporosis model was prepared with injection of dexamethasonc. Antagonism osteoporosis acupoint paste(AOAP) on acupoints and non-neridian places was administrated to compare with oral recipe for kidney tonification in the treatment of osteoporosis. It took the changes in serum estrogen, bone density, calcitonin/parathyroid hormone(CT/PTH), thyrotropic hormone(TSH), free T3 and free T4 as the measuring indexes. Immunocyto-chemistry stain and morphological measurement of TSH cell,follicular adenoma of thyroid gland(C cell) and thyroid globulin(Tg) were applied in pituitary gland and thyroid gland to observe the therapeutic results.MAIN OUTCOME MEASURES: ① Adjustment of the recipe for kidney tonification on thyroid function. ② Adjustment of the recipe for kidney tonification on bone density.RESULTS: AOAP improved the levels of estrogen, CT/PTH, TSH, free T3and free T4, increased bone density. The counts of TSH cell, C cell and Tg positive reaction substance were increased and they were colored deeply.CONCLUSION: AOPA, by "multiple relevant convergence reaction", adjusts and affects systematically the endocrinal function of bone metabolism,improves the levels of estrogen and CT/PTH, reverses the declining tendency of pituitary-thyroid axis function and improves thyroid function so as to weaken osteocyte in the bony absorption, enhance osteoblast in osteogenesis and increase bone density.