| Background:Osteoporosis which was considerd as bone mass diminution characterized by bone mineral reduction and the disruption of bone microarchitecture:bone trabec-ula become thiner,breaked and reduced and integumentale become thiner with incre-ase porosity. Osteoporosis involve constitutional osteoporosis and secondary osteo-porosis. Weightlessness-induced osteoporosis is a secondary osteoporosis,it is a spec-ial disuse osteoporosis caused by the microgravity environment.Weightlessness is the object shows only for the quality but not for the weight in the microgravity (10-6-10-9 g).Research about skeletal system Pathophysiology changes induced by weightlessne-ss indicated that weightlessness evoked astronaut to take place a disuse osteoporosis. Disuse osteoporosis induced by weightlessness mainly manifested ad reduced bone mass,decreased bone mineral, decreased bone mineral density osteoporosis,the mech-anical properties of bone decreased and a negative calcium balance. Aerospace Medi-cine research in microgravity of all physical systems, microgravity to change the im-pact of the metabolic is one of the most serious damage. Aerospace Medicine attaches great importance to the bone metabolism, although a lot of research work, but the reg-ulation of bone metabolism would be disequlibrium and the lost of bone mass might keep developing. Osseous tissue mainly consists of osteogenitor cell,osteocytes, oste-oblasts and osteoclasts.Osteoblasts and osteocytes are the most important mechanical receptive cells in bone tissue.A lot of research indicates that,bone loss induced by m-icrogravity was distinguished by bone formation suppression, declining in the number of osteoblasts,bone mineral dyspoiesis and bone delayed maturity.As the result of os-teoblastes and osteocytes are short of necessary mechanical force stimulated in mic-rogravity environment,tthe number of osteoblasts and osteocytes declined,finally bro-ught into bone formation decrease.The research about bone loss in space flight is foe-us on osteoblasts and osteocytes of the microgravity response,signal transduction, gene expression,functional changes and microgravity on osteoblast differentiation process. As the creation of International Space Station and the implementation of mar-sexplor ation, mankind will lengthen detention time in space. Therefore,strengthens the research of bone metabolism in environment of microgravity,and provides a new thinking prevention and cure in disuse osteoporosis.Currently used for osteoporosis and drug roughly divided into three cate-gories:the first is the absorption inhibitors that have estrogen, calcium phosphate and the vegetarian;the second type are to promote the formation and contains fluoride, vit-amin d, parathyroid hormone, or growth hormone; the third class for a bone is bone absor-btion inhibitors and bone formation promotors,such as strontium salt. To space flight in the disuse osteoporosis, and often have sports in the confrontation approach the exe-rcise, the use of artificial gravity, the body, as well as changes are taking drugs as a calcium phosphate, of these drugs, although a certain effect, but effect a mechanism for a single factor. Strontium Ranelate goods named protelos, france and pharmaceutical company, Servier develop the significance of the new generation to osteoporosis and to reduce the risk of bone fractures osteoporosis, and enhance the area has a certain strength and curative effect. The drug is approvaled the end of in 2004 by EMEA. Strontium Ranelate by a minor element deficiencies strontium and ranalic acids. Strontium is one important component of a skeleton, it can promote the development and formation of such a bone, and have a regulatory role of calcium me-tabolic. In many of the drug treatment for osteoporosis,Strontium Ranelate is the only one can stimulate osteoblast form, and inhibit osteoclast absorbtion.Currently resea-rches of SR focus on postmenopausal osteopoosis and senile osteoporosis far more than weightlessness induced osteoporosis. Using the rat tail suspension model, we studied the effect of Stron-tium Ranelateon osteoblast and bone marrow cells apop-tosis after skeletal unloading.Objective:Using the rat tail suspension model, we studied the effect of Strontium Ra-nelateon osteoblast and bone marrow cells apoptosis after skeletal unloadding.Method:1.Twenty-four male SD rats were randomly assigned to four groups:control group,model group,group of treated with strontium ranelate 3-days before suspension and group of treated with strontium ranelate while suspension.The tails of tail-suspended rats were pasted by ventilated adhesive tape on two sides.The other end of the adhesive tape was suspended by a plastic circle which can move freely along a rod.The head-of rat was kept on low position,and hindlimb unloaded without constraint moving.The control rats were untreated.All the rats were fed equivalence of food without limited drinking in the same cages.2.Observation on rat model:To observe the activities,diet,body weight,colour and luster of hair and tail of rats during tail-suspension.After simulated weightlessness,biochemical markers of bone metabolism were observe-d.Meanwhile,the right tibia metaphysis was processed for histomorphometric analysis.3.Measurement of biochemical markers of bone metabolism:Serum Ca,P,ALP was measured by automatic biochemistry analyzer,BGP measured by radioimmunoassay.4.The condition of cell apoptosis in bone tissues was detected with in situ death detection.5.The expression of Fas in bone tissues was detected with SP immunohistochemical method.Results:1.During tail-suspension,the rats moved,ate freely and did not bite tails.All rats were alive without ischemai and necrosis of tail.And body weight of tail-suspended rats didn't decreased significantly(P>0.05);2.Measurement of biochemical markers of bone metabolism:In the rats of simulated weightlessness groups,serum bone Gla protein,alkaline phosphatasecontent were significantly lower than those in control group (P<0.05), whereas serum calcium,phosphorus concentration were higher than that in control group(P<0.01), Serum bone Gla protein,alkaline phosphatasecontent in Rats in groups of treated with strontium ranelate 3-days before or while suspension were significantly higher than that in model group(P<0.05),whereas serum calcium,phosphorus concentration were higher than that in model group(P<0.01).3.TUNEL examination showed:compared with corresponding control group, tail suspension for 7-days increased apoptosis of osteoblasts and bone marrow cells,there were significantly difference(P<0.01). Apoptosis in rats bone tissue in groups of treated with strontium ranelate 3-days before or while suspension were lower than model group(P<0.01).4.The Fas protein examination demonstrated:compared with corresponding control group, tail suspension for 7-days increased Fas protein expression,there were significantly difference(P<0.01).Fas protein expression in rats bone tissue in groups of treated with strontium ranelate 3-days before or while suspension were lower than model group(P<0.01).Conclusion:1.The rat which simulates microgravity condition by tail suspended succeeds resulting in headward shift of body fluid and unloading of weight-bearing bones which are two main physiological effects under microgravity with little stress.It supplies a good rat model for studies on simulated microgravity condition on land.2.Simulated microgravity affect serum markers of bone metabolism.3.Simulated microgravity increased Fas protein expression.4.Simulated microgravity induces a increase apoptosis in osteoblast and bone marrow cells.5.SR increase the content of ALP and BGP,improve the activity of osteblast and improve the negative balance of calcium in microgravity environment.6.Fas protein expression in rats bone tissue in groups of treated with strontium ranelate 3-days before or while suspension were lower than model group,the former was better than the latter.It accounted that in the early treatment can inhibit Fas expression,reduce the opoptosis of osteoblast,osteocyte in microgravity,and then promote the bone formation. |
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