| Objective:Investigate the relationship between micro-environment changes and PMOP from the perspeetive of hypoxia and acidification,which to provide the objective reasonable quantification and seientific basis for Chinese medicine theory of "blood stasis" in the treatment of osteoporosis.Methods:Clinical Research:60 female patients were selected from the first hospital affiliated to Guang zhou university of Chinese medicine between March 2009 and February 2011, who were diagnosed for bone mineral density. The patients were divided into three groups:patients with postmenopausal osteoporosis in 20 cases (PMOP group), postmenopausal women without osteoporosis and 20 (bone loss group), pre-menopausal women 20 patients (control group). Lateral lumbar vertebral bone mineral density test; serum enzyme-linked immunosorbent assay of hypoxia inducible factor 1α(HIF-1α) and acid-sensing ion channels (ASICs) level.Animal experiments:52 healthy female SD rats were randomly divided into control group for 16 rats and the surgery group for 36 rats.3 months after surgery from two randomly selected 6 of the rats in vivo bone density examination to determine the successful model. After modeling in determining the success, the rest of the surgery group,30 rats were randomly divided into 3 groups,10 in each group were surgical model group, estrogen group, Chinese group. Oral administration further treatment, Chinese medicine group was given by gavage GuKang; estrogen group was given orally nilestriol;blank control group, operation model group were given distilled water. All rats were sacrificed at 5 months, animals were killed 1 day before the line of bone mineral density in vivo, were killed after the collection of blood, preparation of serum for the ELISA (HIF-1αand ASICs)Results:The clinical experimentClinical studies on 60 patients with premenopausal and postmenopausal patients with observation of their bone mineral density, serum HIF-1αand ASICs were detected in serum of postmenopausal women found that HIF-1 a, ASICs content higher than women, PMOP group of HIF-1αlevel was higher (P<0.01), but with the bone loss of HIF-1αgroup showed no significant difference (P> 0.05). PMOP ASICs group was the highest,higher than the control group, and bone loss (P<0.01), bone loss is also higher than the control group ASICs content (P<0.01). Three HIF-1α,ASICs and relevant relationships between BMD, BMD and HIF-1 a levels showed negative correlation(r=-0.681,P<0.01), BMD values and ASICs content showed negative correlation (r=-0.840, P<0.01), while HIF-1αand ASICs showed a positive correlation between levels (r=0.783, P<0.01).The animal experimentAnimal experiments through the establishment of ovariectomized rat model to the experimental drugs GuKang to Nilestriol as a positive control drug, observed GuKang on bone mineral density, serum HIF-1α, the serum levels of ASICs. Operation model group, low BMD than other groups;operation model group before treatment,after treatment, BMD was less than the control group (P <0.05).Estrogen treatment group and TCM group was higher than before treatment BMD BMD (P<0.01). Operation model group, estrogen and Medicines HIF-1αwere significantly higher than the control group (P<0.05),while the Chinese group and the estrogen group were lower than HIF-1αoperation model group (P<0.05). ASICs operation model group was higher than the control group (P<0.05), while the other comparison between groups was no significant difference between ASICs content (P>0.05).BMD after treatment with the HIF-1αlevels showed negative correlation (r=-0.869, P<0.01),BMD after treatment with ASICs content showed negative correlation(r=-0.706, P<0.01), while HIF-1αand ASICs showed a positive correlation between (r=0.846, P<0.01).Conclusion:Animal experiments and clinical research shows GuKang to reduce HIF-1α, ASICs content.Clinical study found that postmenopausal women with serum HIF-1α, ASICs were significantly higher in women. Groups HIF-1α, ASICs, and BMD related to sexual relations between, HIF-1α,ASICs, and BMD positive and statistically significant correlation (P<0.01).Confirmed from the microscopic objective of molecular biology in postmenopausal osteoporosis patients have micro-environment of circulation, there is "Blood stasis" the pathological basis of change. That HIF-1α,ASICs may be directly involved in the process of bone metabolism, may also be through the estrogen or some other intermediary factor indirectly involved in the process of bone metabolism. The exact value needs further study.Serum HIF-1α,ASICs abnormal levels of blood stasis in the formation mechanism for PMOP has important physiological and pathological significance. HIF-1α,ASICs as a specific marker for hypoxia and acidification, one of the development process in PMOP how the relationship between the specific mechanism remains uncertain, pending further study.Thus depth HIF-1α, ASICs in the role of blood stasis in the formation of the internal mechanism and the relevant contact with PMOP can further improve the Integrative Medicine PMOP mechanism of etiology and pathology. |
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