目的探讨补肾方药对骨质疏松的防治作用及其机理.方法本研究选用3种模型,即地塞米松和卵巢切除所诱发的骨质疏松模型,自然衰老的大鼠骨质疏松模型,并给予中药治疗.测定大鼠骨密度、骨代谢相关生化指标及骨形态计量学指标及基因表达分析.结果补肾方药可显著提高地塞米松所致骨质疏松大鼠的骨密度、血清骨钙素水平,降低尿钙排泄,同时,促进骨组织中Ⅰ型胶原和LMP-1 mRNA表达,补肾方药还提高小肠黏膜CaBp-D9K基因表达,从而使小肠黏膜钙结合蛋白(CaBp)的合成增加,促进小肠对钙的吸收;补肾方药可提高卵巢切除所诱发的骨质疏松大鼠的骨密度,促进骨组织中Ⅰ型胶原mRNA及小肠黏膜中VDR mRNA的表达,提高卵巢切除大鼠血清雌激素的水平,同时,提高骨组织中雌激素受体α和β(ERα,ERβ)的表达,增加雌激素对骨代谢的调节作用;补肾方药改善老年骨质疏松大鼠骨代谢,降低尿钙排泄,通过提高骨转换,主要是促进骨形成防止骨量丢失.结论补肾方药通过多环节、多途径,调节骨质疏松大鼠的骨形成与骨吸收,使其达到骨形成与骨吸收相偶联,而防治骨质疏松.
Objective\ To study the preventive effects of kidney\|tonifying Chinese medicinal herbs on rat osteoporosis. Methods\ Dexamethasone (DEX)\|treated or ovariectomized or senile rats were given kidney\|tonifying Chinese medicinal berds(TKM) to protect rats from bone loss.Bone mineral density and bone metabolism\|associated biochemical markers were determined. Bone histomorphometric indexes were assessed and the expression of gene was analyzed. Results\ (1)Kidney\|tonifying herbs (KTH) increased BMD of the DEX\|induced osteoporotic rats, promoted the expression of collagen type Ⅰ and LMP\|1,significantly increased the levels of serum osteocalcin, decreasd the excretion of urine Ca. KTH promoted the expression of CaBp\|D9K gene, which promoted the absorption of Ca in the intestine.(2) KTH protected the ovariectomized rats from bone loss, promoted expression of collagen type Ⅰ and estrogen receptor α and β mRNA in bone tissue and the expression of the vitamin D receptor (VDR) mRNA in the intestine mucosa cells. KTH significantly increased the levels of serum estrogen in the ovariectomized rats. (3) Results of bone histomorphometric study: trabecullar bone volume % (TBV%), trabecullar bone formation surface %(TFS%) and trabecullar bone resorption surface %(TRS%) from senile rats' tibias were lower than those from young rats' tibias. These results suggested that bone metabolism of senile osteoporosis belonged to low turnover. KTH increased TBV%, TFS% and TRS%, decreased the level of urine Ca/Cr in senile rats. KTH promoted bone turnover, but its main effects were to increase bone formation so as to prevent senile rats from bone loss. Conclusion\ KTH modulate the bone formation and bone resorption, facilitating the coupling of bone formation and resorption to prevent bone loss in many ways.
Chinese Journal of Osteoporosis
Kidney\|tonifying chinese medicinal herbs
\ Bone mineral density
\ Gene expression