The Research Of Early Preventing Ovariectomized Rats'osteoporosis With Combined Therapy Composed Of Exerciseand Traditional Chinese Medicine

BackgroundOsteoporosis is recognized as a major health problem with the aging of the population. The number of patients will certainly grow, and there were 2 hundred million peoples suffered with this disease in the world, among these patients, women are occupied by 80% .The estrogen secretions are reduced sharply in postmenopausal women, and the bone metabolism balance are destroyed. Bone formation is decreased, whereas the bone absorption are increased, so the bone mass are gradually lost, and microarchitectural of bone tissue are deteriorated with a consequent increase in bone fragility and susceptibility to fracture. PMO fractures are potentially devastating and associated with high morbidity and substantial economic burden. So how to early prevent and treat PMO is not only a medicine issue, but also a social issue.Because the bone mass loss is gradually and unreversedly, there isn't any method to cure osteoporosis which was happened. So early prevention osteoporosis is more important than cure it. Pharmacologic therapy such as HRT, bisphosphonates, calcitonin, teriparatid are used in the treatment of osteoporosis, but the long-term pharmacologic therapy bring the new risk of phamaco side-effect and the compliance of patients is relatively poor. The ability of estrogen to prevent the rapid bone loss associated with menopause is well accepted. But the use of hormone therapy for postmenopausal bone loss has become controversial given recent data regarding the risks of therapy. So, long HRT therapy is not the first line of the choice of prevention of osteoporosis.Mechanical loading that was transducted by exercise stress changed the pressure of the bone and stimulated the bone formation, increased BMD and improved the performance of the bone biomechanics. And physical activity also increased muscle function, improved body balance as a result, reduced the rate of fall and osteoporonic fractures. Exercise has a positive role in the prevention of osteoporosis. But it was estimated that the exercise of single fashion only improve the local skeleton BMD that exercise muscle attached, and it can't increase the whole bone mass. So, only exercise in the prevention of PMO is inadequate.Chinese medicine showed that the "weak renal" is the basal pathogenesis of OP, and weak renal, weak spleen, blood thrombosis are tale part in the causes of the disease. In clinical , several traditional Chinese herb have positive role in the preventing and treating of OP. But the mechanical of it's curative role in OP was remained unknown. Epimedium is the most use component of the Chinese prescription, which has a role as phytoestrogen. There are several reports that Exercise accompany traditional Chinese herb have an effective role in clinical care of OP. It is unknown in the risk of long therapy of traditional Chinese herb such as Epimedium, especially risk in uterus and breast.Thanks to intense effort in the clinical and research field, important progress have been made in our understanding of the mechanisms by which transcription factors control osteoblastogenesis. A decade ago, Runt and Osx has been identified as the major transcription factors controlling osteoblast commitment and differentiation. The progression of research in transcription factors control osteoblastogenesis establishes the foundation for the development and evaluation of potential anabolic mediators of bone formation. It is unknown weather exercise combined with Chinese medicine can increase the expression of the osteoblast specific transcription factors of the bone tissue.ObjectiveTo explore the influence of exercise combined by traditional Chinese on the bonemineraldensity(BMD), biomechanics performance, uterus weight, and femur proximal tissue Osx mRNA through treating the 3 month old ovariectomised rats models during 12 weeks by different way, including estrogen, exercise only, Chinese medicine GuShuKang only , exercise associated with GuShuKang, and OVX , and SHAM.. To investigated the effect and mechanical of the therapy in early prevention and treatment of postmenopausal; Hope to offer theory evidence to getting better method of preventing and treating postmenopausal osteoporosis.Material and methodsDivided 46 three -month-old female SD rats into 6 groups at random, and these groups were respectively managed by different therapy methods after ovariectomy, such as exercise treatment group (OVX +ET ) which Rats are running on the platform every five day in one week; GuShuKang group (OVX +GSK) Rats were medicined by Chinese medicine only ;exercise associated with GuShuKang group (OVX +ET +GSK); Estrogen group (OVX +ES) rats were medicined by Premarin tablet; two control group (ovariectomy group, OVX; SHAM group). At the seventh day after abdominal ovariectomy, used traditional Chinese medicine supplement therapy, athletics therapy and therapy of athletics plus traditional Chinese medicine supplement to treat the ovariectomized rats expect OVX group. At the end of treatment after 12 weeks, all rats were killed. Body weight and uterus weight were measured immediately. The left femur and the fifth lumbar were submitted to an evaluation of the physical properties and a biomechanical including BMD measured by DXA , ash weight, and the biomechanical properties of the femur were determined using a three-point bending test. The expression levels of osteoblast-related genes Osx mRNA in the right proximal femur tissue measured by real-time PCR. The right distal femur were made in tissue sections , observed after H&E staining.Results1. Body weightThe initial body weight of all the groups was not statistically significant different. However, after 12 weeks, the OVX and Chinese medicine treated OVX rats showed higher body weight values than the sham-operated and estrogen-treated OVX ones. But both the exercised OVX rats and exercise combined by Chinese medicine treated have similar body weight with SHAM ones.2. Uterus weight and serum E2 levelSHAM and OVX+ES rats exhibited the highest Uterus weight and serum E2 level than other groups rats, among other groups of OVX+GSK+ET,OVX+GSK,OVX+ET,OVX, Uterus weight and serum E2 level not statistically significant different.3. Femur ash/dry weight and femur,lumbar BMDOvariectomy rats produced a significant statistical decrease in the femur physical properties when compared to the SHAM and estrogen treated OVX group. Moreover, the results shows that the Chinese medicine treated animals presented significant higher values for ash weight, bone density andmineral density when compared to the sham-operated sedentary animals, indicating the positive effect of GSK on the femur physical properties. No statistically significant difference was observed between OVX and OVX+ET4. Biomechanical propertiesOvariectomy caused a significant decrease in bone strength of the vertebra in osteopenic animals when compared with SHAM and estrogen treated OVX rats. On the other hand, the physical running training produced an increase in Femur maximal load in the OVX exercised animals and in OVX exercised combined by GSK therapy rats when compared to other intervened animals .5. bone tissue section H&E stainingBone marrow cavity are wider and occupied by more adipocytes cell in OVX rats than in SHAM and estrogen treated OVX rats, both Chinese medicine threatment and ecercise combined with Chinese medicine threatments can ameliorate the morphologic observation of the bone tissue sections.6. Osx mRNA in femur proximal tissue measured by quantitative realtime PCRThe expression level of Osx mRNA in femur proximal tissue from OVX rats was significantly lower than that of SHAM , OVX+ES, OVX+GSK, OVX+GSK+ET rats. While among other groups Osx mRNA expression isn't different .Conclusion1. Exercise combined with Chinese medicine therapy can inhibited the bone loss in rat ovariectomied osteoporosis model, ameliorated the Biomechanical properties, but didn't stimulate the uterus.2. Exercise therapy can inhibited body weight gain caused by low estrogen in ovaryectomy rat.3. Running can improve the femur biomechanical properties and resulted in decreaseing in susceptibility to fractures4.Exercise combined with Chinese medicine stimulate bone formation through increasing the expression of the osteoblast specific transcription factors of the bone tissue...