目的 观察藿骨牡蛎方对肾阳虚型绝经后骨质疏松症(postmenopausal osteoporosis，PMOP)大鼠骨密度及激素水平的影响。方法 选取48只雌性SD大鼠随机分为假手术组，模型组，强骨组，碳酸钙组，低、高剂量组，每组8只。适应性喂养后，除假手术组外，大鼠以双侧卵巢去势手术建立模型，假手术组切除卵巢附近等体积脂肪，利用阴道涂片判定去势手术成功后，各组给予相应药物或溶剂灌胃90 d，末次灌胃后麻醉、采集样本。应用Micro CT检测大鼠骨密度(bone mineral density，BMD)、骨矿含量(bone mineral content，BMC)、骨小梁数量(Tb。N)、骨小梁厚度(Tb。Th)、骨小梁分离度(Tb。Sp)和结构模型指数(structure model index，SMI)，观察松质骨显微结构及子宫HE染色，应用ELISA检测血清Ca、尿Ca及促肾上腺皮质激素(adrenocorticotropic hormone，ACTH)、皮质醇(cortisol，CORT)、环磷酸腺苷(cyclic adenosine monophosphate，cAMP)、环磷酸鸟苷(cisco group management protocol，cGMP)、雌二醇(estradiol，E2)、雌二醇受体α(estrogen receptor，ERα)。结果 与假手术组比较，第17天模型组大鼠体质量明显升高(P＜0。05);BMD、BMC、Tb。Th、Tb。N、E2、ERα、CORT、ACTH、cAMP、cAMP/cGMP明显下降(P＜0。05)，Tb。Sp、SMI、尿Ca、cGMP明显升高(P＜0。05)，骨小梁变薄，结构松散，部分样本出现断裂;子宫明显萎缩，宫腔缩窄，细胞缩小，排列松散。与模型组比较，藿骨牡蛎方低剂量组大鼠体质量增长在第24～31天间明显减慢(P＜0。05);藿骨牡蛎方低、高剂量组大鼠BMD、BMC、Tb。Th、Tb。N、E2、ERα、ACTH、cAMP、cAMP/cGMP明显升高(P＜0。05)，Tb。Sp、SMI、尿Ca、血清Ca、cGMP明显降低(P＜0。05)，骨小梁结构完整、数量增加，子宫体积及宫腔面积明显增加，细胞形态及腺体数量改善。结论 藿骨牡蛎方可以显著提高肾阳虚型PMOP大鼠骨密度、保护股骨微结构、减少骨矿物质流失、调节骨代谢水平，提示藿骨牡蛎方具有防治PMOP的作用。同时，藿骨牡蛎方能够提高E2 和ERα水平，能够提高ACTH水平并调节cAMP、cGMP水平，对抗肾上腺轴的衰退，改善肾阳虚状态，表明藿骨牡蛎方具有"益癸培元、补肾强骨"功效，能够改善肾阳虚型PMOP。
Effects of the Huogumuli Formula on bone density and hormone levels in rats with kidney yang deficiency-induced postmenopausal osteoporosis
Objective To observe the effects of the Huogumuli Formula on the bone density and hormone levels in rats with kidney yang deficiency-induced postmenopausal osteoporosis(PMOP).Methods Forty-eight female SD rats were randomly assigned to six groups:sham operation group,model group,strong bone group,calcium carbonate group,low-dose group,and high-dose group,with 8 rats in each group.After adaptive feeding,a rat model was established by performing bilateral ovariectomy surgery on all groups except the sham operation group.In the sham operation group,an equal volume of adipose tissue adjacent to the ovaries was removed.The assessment of a successful ovariectomy surgery was based on vaginal smears.Subsequently,the respective groups were intragastric with corresponding drugs or solvent for 90 days.Anesthesia and sample collection were performed after the final intragastric administration.Micro CT was employed to detect bone mineral density(BMD),bone mineral content(BMC),trabecular number(Tb.N),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and structural model index(SMI)in rats.The cancellous bone microstructure and uterine HE staining were observed.The serum levels of calcium(Ca),urinary calcium(uCa),adrenocorticotropic hormone(ACTH),cortisol(CORT),cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),estradiol(E2),and estrogen receptor alpha(ERα)were measured using ELISA.Results Compared to the sham operation group,the rats in the model group exhibited a significant increase in body weight on day 17(P<0.05).Moreover,there was a significant decrease in the levels of BMD,BMC,Tb.Th,Tb.N,E2,ERα,CORT,ACTH,cAMP,and cAMP/cGMP(P<0.05),while a significant increase in the levels of Tb.Sp,SMI,uCa,and cGMP(P<0.05).Histological analysis revealed a thinning of trabecular bone and a loosening of structure,with some samples showing fractures.Significant uterine atrophy,narrowing of the uterine cavity,cell shrinkage,and loose cell arrangement were observed.Compared to the model group,the low-dose group of Huogumuli Formula showed a significant deceleration in body weight gain between days 24 and 31(P<0.05).Both the low-and high-dose groups of Huogumuli Formula exhibited a significant increase in the levels of BMD,BMC,Tb.Th,Tb.N,E2,ERα,ACTH,cAMP,cAMP/cGMP(P<0.05),while a significant decrease in the levels of Tb.Sp,SMI,uCa,Ca,cGMP,and the trabecular structure of bone was intact and the number increased,the uterine volume and uterine cavity area increased significantly,and the cell morphology and the number of glands improved.Conclusion Huogumuli Formula significantly improves bone density,protects femoral microstructure,reduces bone mineral loss,and regulates bone metabolism in rats with kidney yang deficiency-induced postmenopausal osteoporosis(PMOP),indicating its therapeutic potential in the prevention and treatment of PMOP.Additionally,Huogumuli Formula increases the levels of E2 and ERα,enhances the ACTH level,and improves the cAMP and cGMP levels,thereby counteracting the decline of the adrenal axis and improving the kidney yang deficiency.These findings suggest that Huogumuli Formula exhibits efficacy in nourishing the essence and strengthening the kidney,ultimately improving kidney yang deficiency-induced PMOP.
postmenopausal osteoporosis(PMOP)Huogumuli Formulaestrogenkidney yang deficiency
万方数据
维普
