| ObjectiveTo analyze the clinical baseline information, BMD and bone turnover markers of Kidney-Yin deficiency, and kidney-Yang deficiency in PMOP, and to explore the difference of the two TCM syndromes.Based on the synthesis and cross-linking of collagen type I and the mineralization of bone matrix, to explore the efficacy and intervention mechanism of tonifying kidney yin and tonifying kidney yang in PMOP.MethodsThe PMOP patient who were hospitalized in The First Affiliated Hospital of Guangdong University of Chinese Medicine, and were diagnosed as Kidney-Yin deficiency syndromeand kidney-Yangdeficiency syndrome by diagnostic criteria of TCM syndromes. The age, age of menopause, menopausal period, weight, height, BMI of the patient were collected and the BMD, T value, bone turnovers (PINP, β-CTX, N-MID and 25-OH Vitamin D) were detected. The difference of baseline information and measurement parameters between the two syndrome were analyzed with independent-samples T test.One hundred and fifty female SD rats were divided into five groups, the sham group, the model group, the western medicine group, the tonifying kidney-yin group and the tonifying kidney-yang group. The OVX models were established, and three months after the operation, the lavage intervention was conducted. In western medicine group, the Fosamax was used; in tonifying kidney-yin group, the Liu Wei Di Huang Pill was used; in tonifying kidney-yang group, the Guifu Dihuang Pill was used; in the sham and the model groups, normal saline was used. Three months after the intervention, the experiment measurements were explored. The BMD of proximal femur were detected with Lunar dual energy X-ray absorptiometry; the histomorphology changes of proximal femur were observed by HE stain of bone paraffin section; the bone turnovers(B-ALP, PINP, NTX, and CTX) were determined with Elisa; the related genes that regulating synthesis(COLIA1, COLIA2) and cross-linking(Lhx9) of collagen type I and the mineralization of bone matrix(Bglap, Ibsp, Smad3, Runx-2) were detected with RT-PCR. The differences of the measured indicators among groups were analyzed with one-way analysis of variance.ResultsSixty-one Han’s PMOP patient were included,28 cases were kidney-yin deficiency syndrome and 33 cases were kidney-yang deficiency syndrome. The difference of age, menopause age, menopausal period, weight, height and BMI between two groups were detected with independent-samples T test, and the result reveled that there was no significant difference of baseline data between the two groups (P>0.05). The BMI=25 was set as classification criterion, and the number of overweight cases in kidney-yin group were significantly larger than that of kidney-yang group(P＜0.01). The difference of BMD and BMC between the two groups were determined with independent-samples T test, and there were no significant difference of BMC(P>0.05), but the BMD in kidney-yin group was significantly higher than that in kidney-yang group(P＜0.05). The contents difference of β-CTX, N-MID and 25-OH Vitamin D was not significant(P>0.05). The concentration of PINP in kidney-yin group was significantly higher than that in kidney-yang group(P＜0.05).After OVX, the BMD in the model group was significantly lower than that in the sham group(P＜0.05), by the intervention of experimental medicine, the BMD in the three intervention group was significantly higher than that in the model group(P＜0.05), and there was no significant difference of BMD between tonifying kidney yin group and tonifying kidney yang group(P>0.05). Comparing to the sham group, in the model group, the trabecular number was decreased, and arranged irregularly, the separations were enlarged, and there were missing osseous unions caused by breakdown. After the intervention of the three types of medicine, the trabecular number was increased, and arranged regularly, the separations were narrowed and there was no obvious breakdown. Comparing with the sham group, the expression of Lhx9 in the model group was significantly decreased(P＜0.05). In the intervention groups, the expression of COLIA1 in tonifying kidney-yang group was significantly higher than that in the sham group(P＜0.05), the COLIA2 expression in western medicine group and tonifying kidney-yin group was significantly increased than that in the model group (P＜0.05). The expression of Lhx9 in tonifying kidney-yang group was significantly higher than that in the model group(P＜0.05). Comparing to the western medicine group, the expression of COLIA1 and Lhx9 in tonifying kidney yang group was significantly increased (P＜0.05). Comparing with tonifying kidney-yin group, the expression of COLIA1 and Lhx9 was significantly increased (P<0.05), but the expression of COLIA2 was significantly decreased(P＜0.05). To compared with the sham group, the expression of Bglap and Runx-2 in the model group was significantly decreased(P＜0.05). Comparing to the model group, the expression of Bglap in the western medicine group and the tonifying kidney-yang group was significantly increased (P＜0.05), and the expression of Ibsp in tonifying kidney-yin group was significantly increased(P＜0.05), the expression of Smad3 in these three groups were all significantly increased(P＜0.05). The Bglap expression in tonifying kidney-yang group was significantly higher than that in tonigying kidney-yin group(P＜0.05), and the expression of Ibsp was significantly decreased(P＜0.05).ConclusionThe BMI, BMD and bone turnovers of kidney-yin deficiency syndrome and kidney-yang deficiency syndrome in PMOP patient were significantly different. The overweight and elevating bone formation rate may the reason that why BMD in kidney-yin deficiency patient was higher than that in kidney-yang deficiency patient.Both tonifying kidney yang and tonifying kidney yin are efficacy in treating rat postmenopausal osteoporosis by modulating bone metabolism and regulating gene expressions of type I collagen synthesis, crosslink and matrix mineralization related gene, but the mechanism of two treatments are different. |
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