The Synergistic Effect Of Microwave Radiation And Hypergravity On Rat Bone Metabolism And The Correlated Mechanism

The thermal effect of microwave radiation may cause death, disability, or injury to organisms upon the diversity of radiant intensity, time and space, and it has attracted more and more concerns due to the catholicity and complexity of the injury. The phenomena of microwave radiation and hypergravity are increasing in daily life. Microwave Thermotherapy has been gradually used in radiotherapy, furthermore, with the advent of long term interplanetary missions, space biology is becoming an emerging area of research devoted to assess the effects of altered gravity conditions and microwave radiation on human health, and the current research focus has shifted to the two-factor synergistic effect on body. The damage of microwave radiation and the harm of hypergravity to organisms have been confirmed respectively, but there are very few reports on the synergistic effect of microwave radiation and hypergravity, and there is no report on the role of Rana sylvatica Le conte oil as a radioprotector.A replication animal model was selected to investigate the synergistic effect of microwave radiation and hypergravity and the intervention effect of Rana sylvatica Le conte oil on rats, and then some indexes were detected. The results show that the motion and nervous system of rat might be affected critically by the synergistic effect of microwave radiation and hypergravity, for the climbing pole height and the activities of serum ChAT and ChE decrease significantly. Furthermore, the synergistic effect of microwave radiation and hypergravity causes damage to most rat organs, such as the liver, heart, kidney, and skeletal muscle, so the activities of ALT, AST, CK, ICDH, HBDH, and the concentration of BUN increase apparently, and the antioxidant effect might also be damaged, for the T-AOC of rat serum decreases significantly, while the injury resulted from it can be protected by intervention with Rana sylvatica Le conte oil.The experiment was designed to investigate the effect of microwave radiation on osteogenesis and osteolysis of rats in the hypergravity condition and to observe the role of Rana sylvatica Le conte oil and spinacene as radioprotectors, and then the correlated indicatrices of bone metabolism were detected. The results demonstrate that the concentrations of osteocalcin and calcitionin and the activity of ALP in serum and bone tissue decrease after the synergistic effect of microwave radiation and hypergravity. The concentrations of calcium and phosphorus in serum increase, while those in bone tissue decrease after the synergistic effect of microwave radiation and hypergravity. The synergistic effect of microwave radiation and hypergravity also causes the increase of hydroxyproline concentrations, while the activies of TRACP and ACP decrease in serum and bone tissues. These results imply that the synergistic effect of microwave radiation and hypergravity causes bone metabolic disturbance by inhibiting the osteogenesis and by enhancing the osteolysis, and also by reducing the raw material of bone calcification in rats. The injury resulted from microwave radiation and hypergravity can be protected by intervention with Rana sylvatica Le conte oil and spinacene, while the effect of Rana sylvatica Le conte oil is better than that of spinacene.It has gradually become a hot spot of research that the effect of microwave radiation on cellular signal transduction. It is reported that the damage of microwave radiation to cellular signal transduction pathways including MAPKs, JAK/STAT, PKC, GPCR, GluR, and NF-κB signaling pathways, but there is still no such reports about the BMP/LIMK signaling pathway. BMPs regulate multiple cellular processes, including cell differentiation and migration, and their signals are transducted by kinase receptors of BMPR, while further analysis has revealed that the interaction between LIMK1and the tail domain of BMPR-II in cells inhibited the ability of LIMK1to phosphorylate cofilin. Cofilin is the only known substrate of LIMK1in cells, and it is one of actin depolymerization factor proteins which can reinforce actin motion and help cell movement and chemotaxis. Actin maintains cell shape and polarity, promotes cell migration and cytokinesis by dynamic changing about depolymerization and repolymerization, and participates in various physiological and pathological processes like embryogenesis, organogenesis, and so on. To identify the molecular biological mechanism of the synergistic effect of microwave radiation and hypergravity on bone metabolism, the BMP/LIMK1signaling pathway was selected to be investigated, and the effect of Rana sylvatica Le conte oil and spinacene was observed as radioprotectors. The results show that the protein concentrations and gene expressions of BMPs and BMPR Ⅱ decrease during the synergistic effect of microwave radiation and hypergravity which cause the activation of LIMK1on the downstream of this signal transduction pathway, and thus the concentration of p-LIMK1and the content of p-cofilin increase which destroy the balance between the phosphorylation and dephosphorylation of cofilin, so it affects the distribution and aggregation of the cytoskeleton which inhibits the proliferation and differentiation of osteoblasts and osteoclasts, thereby destroying the balance of bone metabolism. The decrease of BMPs and BMPR Ⅱ concentrations and the activation of LIMK1and cofilin resulted from microwave radiation and hypergravity can be protected by intervention with Rana sylvatica Le conte oil and spinacene, while the effect of Rana sylvatica Le conte oil is better than that of spinacene.This study reports the synergistic effect of microwave radiation and hypergravity on bone metabolism and the injury can be protected by intervention with Rana sylvatica Le conte oil for the first time. Furthermore, this finding reveals the mechanism of the synergistic effect of microwave radiation and hypergravity from the BMP/LIMK1signal transduction passways for the first time. It provides references to the deep study of radioprotection in the hypergravity environment for the clinical orthopedics, and it supplies theoretical supports and experimental basises not only for the investigation of etiological factor and the prevention and cure measures to common diseases such as osteoporosis, but also for the research of concrescence of bone injury.