背景:根据"体表穴位-经络-内脏-靶器官"相关,采用外贴穴位和口服药物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"的特异性呢?目的:本实验将补肾方药分别制成"外贴剂"和"口服剂",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、雄激素受体,观察"归经与受体"的相关性,探讨补肾方药对实验性骨质疏松骨细胞"阳杀阴藏"的影响.设计:以骨质疏松大鼠为观察对象,完全随机,补肾方药不同给药途径的对照实验.单位:河北医科大学中医学院方剂教研室和生化教研室,石家庄市桥东区医院中医科.材料:实验于2004-06/2005-05在河北医科大学中西医结合基础实验室完成.选择3月龄清洁级SD大鼠120只,随机分成6组:正常对照组、病理模型组、补肾方药口服组、外贴膀胱经组、外贴肾经组、外贴非经非穴位组,每组雌雄各10只.补肾方药主要含有骨碎补总黄酮、淫羊藿甙,每克流浸膏含生药量为9.543 g.抗骨松穴位贴剂由熟地、丹皮、淫羊藿等组成.方法:除正常对照组外,其余5组均注射地塞米松建立骨质疏松模型.正常对照组和病理模型组不给药;补肾方药口服组将补肾方药总成分按0.8 g/100 g体质量灌喂给药;外贴膀胱经组大鼠在膀胱经选肾俞、飞扬穴贴敷抗骨松穴位贴剂;外贴肾经组大鼠在肾经选太溪、大钟穴贴敷抗骨松穴位贴剂;外贴非经非穴位组大鼠在大腿内侧肌肉丰厚处选非经非穴位贴敷抗骨松穴位贴剂.给药13周后处死大鼠,放射免疫分析法检测各组大鼠血清雌二醇、睾酮、降钙素、甲状旁腺素的浓度以及骨组织形态计量动、静态参数的变化.主要观察指标:①给药后各组大鼠雌二醇、睾酮、雌二醇/睾酮、骨密度、降钙素、甲状旁腺素、降钙素/甲状旁腺素的测定结果.③给药后各组大鼠骨组织静、动态参数的测定结果.结果:实验选用120只大鼠,全部进入结果分析.①给药后各组大鼠生化指标的测定结果:与正常对照组比较,病理模型组、外贴非经非穴位组雌二醇、睾酮、雌二醇/睾酮、骨密度、降钙素、降钙素/甲状旁腺素均显著降低(P＜0.01),甲状旁腺素均显著升高(P＜0.01);补肾方药口服组、外贴膀胱经组、外贴肾经组以上各项指标均无明显变化(P均＞0.05).②给药后各组大鼠骨组织静、动态参数的测定结果:与正常对照组比较,病理模型组、外贴非经非穴位组骨小梁体积百分比、骨小梁表面百分比、骨小梁形成表面百分比、活性生成面百分比、骨小梁矿化沉积率、纵向骨生长率、骨小梁骨生成速率均显著降低(P＜0.01),骨小梁吸收表面百分比均显著升高(P＜0.01);补肾方药口服组、外贴膀胱经组、外贴肾经组以上各项指标均无明显变化(P均＞0.05).结论:抗骨松穴位贴剂可抑制骨吸收、促进骨形成,有效控制进入血液循环的药量,与口服给药途径取得了同等的药效,拮抗实验性骨质疏松"破骨大于成骨",逆转"阳杀阴藏"的过程,使破骨细胞的骨吸收减弱,成骨细胞的骨形成能力增强,增加骨密度,实现"穴位经络通道的放大效应".%BACKGROUND: According to correlation of "acu-points-meridians-viscera-target-organs", two administration ways of acu-point application and oral medication have been used to treat osteoporosis, both ways can effect via "kidney-meridian tropism"; however whether there is a specificity of target-administration?OBJECTIVE: To investigate the effect of different administration ways of kidney-strengthening remedy on "yang abating and yin hoarding" of osteocytes in experimental osteoporosis by observation the correlation between "receptor and meridian-tropism".DESIGN: A randomized and controlled trial of different administration ways of kidney-strengthening remedy, taking rats with osteoporosis as subject.SETTING: Departments of Prescription Science and Biochemistry of Traditional Chinese Medicine (TCM) Collage, Hebei Medical University, and Qiaodong District Hospital of Shijiazhuang City.MATERIALS: The experiment was completed from June 2004 to May 2005 at the Laboratory of Integrative Medicine Basis of Hebei Medical University. Totally 120 SD rats, aged 3 months and of clean grade, were at random divided into 6 groups: normal control, pathological model, kidney strengthening, bladder meridian application, kidney meridian application and non-special application groups, with either sex being 10 in each group.The kidney strengthening remedy mainly consisted of fortune's Dry Naria Flavoniods and Icarine, each gram of fluid extract contained 9.543 g of the crude drug. The application recipe for anti-osteoporosis consisted of Radix Rehmanniae Praeparata, Cortex Moutan Radicis, Herba Epimedii, etc.METHODS: Except for those in normal group, the rats in the other groups were all given injection of dexamethasone to set up the osteoporosis models. The rats in normal control and pathological model groups were not given medicine, the rats in kidney strengthening group were by gavage given kidney strengthening remedy at 0.8 g/100 g wet. The rats in bladder meridian group were treated by anti-osteoporosis application at the points of Shenshu (BL 23) and Feiyang (BL 58) of the bladder meridian; the rats in kidney meridian group were treated by anti-osteoporosis application at the points of Taixi (KI 3 23) and Dazhong (KI 4) of the kidney meridian;and the rats in non-special application group were treated by anti-osteoporosis application at the areas of non-point-meridian. After 13 weeks administration, the rats were put to death, the concentrations of serum estradiol, testosterone, calcitonin and parathyroid hormone were detected with radio-immunoassay, and both the dynamic and static status parameters about bone morphosis were also measured.MAIN OUTCOME MEASURES:① Estradiol,testosterone,estradiol/testosterone, bone mineral density, calcitonin, parathyroid hormone, and calcitonin/parathyroid hormone of rats in each group after administration ② Both the dynamic and static status parameters about bone morphosis of rats in each group after administration.RESULTS: All rats involved in the trial entered the final result analysis.① The results of biochemical indexes of the rats in each group after administration: Compared with normal control group, the levels of estradiol,testosterone, estradiol/testosterone, bone mineral density, calcitonin and calcitonin/parathyroid hormone of the rats in pathological and non-special application groups after administration were remarkably decreased (P ＜ 0.01), but the level of parathyroid hormone was obviously increased (P ＜ 0.01); however for the levels of the above indexes of rats in kidney strengthening, bladder meridian application and kidney meridian application groups there were obvious changes (all P ＞ 0.05).② The results ofdynamic and static status parameters about bone morphosis of rats in each group after administration: Compared with normal group, in pathological and non-special application groups the volume percentage of bone trabecula, surface percentage of bone trabecula, formation surface percentage of bone trabecula, activity formation surface percentage of bone trabecula,mineralization deposition rate of bone trabecula, longitudinal bone growth rate, and velocity of bone trabeculation were all decreased (P ＜ 0.01), but the absorbance surface percentage of bone trabecula remarkably increased (P ＜ 0.01); however for the levels of the above indexes of rats in kidney strengthening, bladder meridian application and kidney meridian application groups there were obvious changes (all P ＞ 0.05).CONCLUSION: The anti-osteoporosis application can inhibit bone absorption and promote bone formation. It can be effectively controlled in quantity of drug entering the blood circulation, and with the same effect as that given orally. It can check the state of "bone destruction being more than bone formation" in osteoporosis, reverse the process of "yang abating and yin hoarding", making the bone absorption of osteoclast decrease, and the ability of the bone formation of osteoblast increase, enhancing bone mineral density, so that the "amplifying effect of point-meridian-passageway" comes into play.
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