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The Experimental Study On Bushen Zhuanggu Medicine For Treatments Of Glucocorticoid-induced Osteoprosis

Posted on:2011-01-31Degree:MasterType:Thesis
Country:ChinaCandidate:L P LiuFull Text:PDF
GTID:2154360308970082Subject:Science of endocrine and metabolic diseases
Abstract/Summary:PDF Full Text Request
Background:Glucocorticoid (glucocorticoid, GC), because of their important and effective immunosuppressive and anti-inflammatory effects it have been widely used in anti-graft rejection, autoimmune diseases, infection, cancer treatment and other medical fields. However, glucocorticoid-induced bone loss has been reported to occur in up to 50% of patients who require long-term therapy. It is the most common form of secondary osteoporosis, when compared with the postmenopausal osteoporosis and senile osteoporosis, the incidence occurs in third place, therefore, an effective drug to combat this disease, is urgently needed in modern medicine so as to resolve important issues relating to bone diseases. At present, the Western medicine treatment mainly major in the application of calcium preparations, like Vitamin D, bi-phosphate, estrogen, calci-tonin, parathyroid hormone, etc. But they are expensive, and a number of cases have proven with side effects and are not suitable for long-term use, and long-term efficacy is not assured. In recent years, research with glucocorticoid-induced osteoporosis made great contribution in chinese medical mechanism understanding and helped to into finding new medicine to regulate osteoporosis and will further help in finding out new treatment for medicine of this disease.Chinese Bushen Zhuanggu medicine (Xianlinggubao capsules) which is made from epimedium, Radix Rehmanniae, psoralen, Dipsacaceae, Salvia, and Anemarrhena is a composition of several Chinese herbal medicines together. Studies have shown that the main component of the monomer icariin Epimedium can promote osteoblasts (osteoblast, OB) differentiation and mineralization, and can promote the differentiation of bone marrow stromal cells to OB, and works at the gene level to promote BMP-mRNA and Runx-2 gene expression, thus promoting the role of bone formation. It has proven its clinical importance in postmenopausal osteoporosis have a good therapeutic effect. But prevention and treatment of glucocorticoid-induced osteoporosis is still at its infancy stage. Establishing a glucocorticoid-induced osteoporosis model will help to observe the efficacy of GIO and to explore its mechanism of action, with a view to further enrich the prevention and treatment of osteoporosis in theoretical and experimental basis.Objective:TO evaluate the effects of Chinese BUShen Zhuanggu medicine treatment on glucocorticoid-induced osteoprosis rats by means of DEXA, bone biomechanics, biomechanical properties.Methods:Fourty 3.5-month-old female SD rats were randomly divided into 4 equal groups: the control group (group A), the GC-treated group (group B), the treatment with Chinese Bushen Zhuanggu medicine (group C), and bi-phosphate group(group D). In this study, osteoporosis was induced by subcutaneous injection with methylprednisolone 3.5mg/kg per day for 9 weeks. The group C rats were treated with methylprednisolone and in combination with Chinese medicine 150mg/kg per day twice stomach for 9 weeks, the group D rats were treated with methylprednisolone and in combination with bi-phosphate 1.0mg/kg per day once stomach, while another two groups were given the same dose of normal saline. At the end of the 9-week experiment, the indices such as bone mineral density(BMD), biomechanics parameters, bone metabolic markers were measured. Statistical methodsAll data were reported as mean±standare error, SPSS 13.0 software was used for these analyses. One-way analysis of variance (ANOVA) with a LSD test was used to anlysis the changes of rats in different groups and when significance was revealed (P<0.05)Results:1. Osteoporosis model established by glucocorticoid:At the end of the 9-week experiment, The indices of bone formation markers such as serum BGP (0.92±0.31 ng/ml vs. 1.52±0.45ng/ml), serum CT (170.52±29.67pg/ml vs. 211.27±32.31pg/ml) lower than in the group A (P<0.05); The indices of bone resorption markers such as serum TRACP (27.67±7.99 U/L vs. 13.76±2.31U/L) higher than in the group A (P<0.01); Serum Ca (0.98±0.17 mmol/L vs. 1.27±0.25mmol/L) lower than in the group A (P<0.01), serum estradiol (15.47±2.98pg/ml vs. 21.33±4.17pg/ml) lower than in the group A (P<0.05), serum P content (1.27±0.25 mmol/L vs. 1.84±0.50 mmol/L) were not found significant difference in two groups (P> 0.05); The BMD of the femur (0.246±0.012g/cm2 vs. 0.263±0.012g/cm2),and the BMC (0.42g±0.44g) lower than in group A (P<0.05);The BMD of lumbar spine (0.240±0.013g/cm2 vs. 0.572±0.011g/cm2) and the BMC (0.08g±0.27g) lower than in group A (P<0.05); The cortical bone biomechanical property such as max load (217.43±22.27 N vs. 268.67±15.55 N) and rigidity (229.84±80.90 N/mm vs. 322.30±38.54 N/mm); and the max load(124.55±14.65 N vs.150.04±19.85 N) and rigidity (176.39±36.16 N/mm vs. 260.11±71.44 N/mm) of femoral shaft three-point bending test lower than in group A (P<0.05), It were shown that the glucocorticoid osteoporosis model was established successfully.2. Effects of Traditional Chinese medicine on glucocorticoid-induced osteoporosis rats:(1) Changes of weight:At the experiment of 3 weeks, the body weight of the rats in group B, C, D lower than in group A,there was significant difference (P=0.000); but significant differences were not found in three groups. (2) Changes of BMD:In DEXA BMD measurements of the femur and lumbar spine were found significant differences in all groups (F=3.528,5.820; P=0.008,0.003). Group B were significantly lower than in group A (P=0.008,0.001); Group C, D higher than the in group B (P=0.047,0.007; 0.008,0.001), but no significant difference between group C and group D (P=0.453,0.567); The BMC measurements of the femur and lumbar spine were found significantly differences in all groups (F= 7.869,13.088; P=0.000,0.000); Group B were significantly lower than in group A (P =0.000,0.000); Group C, D higher than the in group B (P=0.001,0.001; 0.000, 0.000), but no significant difference between group Cand group D (P=0.851,0.936). (3) Biochemical markers of bone:The indices of bone formation markers such as serum BGP, CT, TRACP and serum Ca, E2 there are differences were found significant differences in all groups.(F= 6.542,4.406,18.057,5.880,6.228; P= 0.001,0.010,0.000,0.002,0.002), Compared with the group A, the levele of serum BGP, CT, Ca, E2 were decreased significantly in the group B, (P=0.008,0.004,0.004, 0.003,0.002), but TRACP were increased in group B. Compare with group B, The levele of BGP, CT, Ca, E2 were increased significantly in the group C, (P=0.003, 0.012,0.005,0.009), the levele of serum TRACP were decreased in group D (P= 0.003), but no significant difference between group A and group D (P=0.006). Serum P content were not found significant difference in all groups. (P> 0.05).(4) The cancellous bone biomechanical property like the max load and rigidity of vertebral body compression test were found significant differences in four groups (F =12.227,4.397; P=0.000,0.010). Group B were significantly lower than in group A (P=0.000,0.004); Group C, D were significantly higher than in group B (P= 0.000,0.000; 0.005,0.007), but no significant differences between the two groups(P= 0.896.0.953); The cortical bone biomechanical property such as the max load, and rigidity of femoral shaft three-point bending test, four groups were found significant differences(F=5.044,4.967; P=0.005,0.006),. Group B were significantly lower than in group A (P=0.008,0.003; 0.005,0.003); Group C, D were sinificantlly higher than in group B (P=0.012,0.007), but no significant differences between the two groups (P> 0.05); Conclusion:1, Bone formation, BMD and bone mass decreased, accompanied with decreased of biomechanical competence. The rat osteoporosis models were successful established.2, Chinese herbs has a powerful effect on preventing glucocorticoid-induced osteoprosis rats. Chinese prescription can effectively improve the bone metabolic markers and the biomechanical property of GIO rats.
Keywords/Search Tags:Glucocorticoid, Osteoporosis, Chinese herbs, bone mineral density, Biochemical indices, Biomechanical property
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