Effects Of Valproic Acid And Adiponectin On Bone Mineral Density In Diabetic Nephropathy Rats

Adiponectin is Cytokine that is secreted by adipose cells.It may be plays an important role in bonemetabolism. DN can affect bone density in different links, which leads to the occurrence of osteoporosis. Inpatients with DN, Adiponectin is proportional to the volume of urine protein and the progression ofdiabetes. Adiponectin as a main factor affecting bone metabolism, it has effects on the D0.but It has notbeen reported. OPG is one of the major components protien of bone mineral density(BMD). The expressionreduction of OPG represents the damage of the bone mineral density. Valproic acid (VPA) could inhibitadiponectin mRNA expression, decreased plasma adiponectin levels, thereby indirectly reduced effects onbone mineral density due to an increase in adiponectin. It play an important protective role inosteoporosis,but the specific mechanism is still not completely clear. We will observe the expression ofAdipoR1and OPG in bone of Do and the effects of Valproic acid, and to explore the mechanism ofadiponectin taking part in the occurrence and development of DO and the possible mechanisms of Valproicacid to protect the bone, in order to provide theoretical basis for the pathogenesis, prevention and treatmentof DO.Objective: To observe the expression of plasma adiponectin,AdipoR1and OPG in bone tissue of DNmodels rat,and the change after the intervention of Valproic acid and adiponectin. in order to find the effctof adiponectin in the development of DO and the mechanism of Valproic acid for protecting DO.Methods: The DN models were established by a single intraperitoneal injection of streptozotocin(STZ).The DN model rats were randomly divided into three groups: DN model group without treatment (n=8), Adiponectin-treated group(APN)(n=8). Valproic acid-treated group(VPA)(n=8) In addition,thenormal rats served as a normal control group (n=9).The APN rats were gavage of Adiponectin (10ug/kg ofbody weight) once a day,10day. The VPA rats were gavage of valproic acid (4ug/kg of body weight) oncea day,7day. the normal control group and the DN model group rats were gavage of identical volum ofdrinking water daily. The test time lasted for16weeks, then determinate the urine of24hours, the volumeof urinary protein and renal function markers, blood calcium,serum phosphorus,alkaline phosphatase.Thenobserved the expreesion AdipoR1and OPG by immunohistochemistry ABC method. Results:(1) The DN model group rats compare with normal control group rats, the24hours urinaryprotein quality, alkaline phosphatase and the expression of AdipoR1in bone tissue significantlyincreased(P <0.01), while the kidney function and the expression of OPG in bone tissue is decreased (P<0.01); and trabecular bone thinning, arranged in disorder, part of the fracture, the bone marrow cavity.(2)The APN group compare with DN model group,24hours urinary protein quality, blood calcium, alkalinephosphatase,and the expression of AdipoR1in bone tissue significantly increase (P <0.01), but theexpression of OPG in in bone decreased (P <0.01), and trabecular bone thinning, arranged in disorder, mostinterrupt, bone marrow cavity widening.(3) The VPA group compare with the APN group,24hours urinaryprotein quality, blood calcium, alkaline phosphatase and the expression of AdipoR1in bone tissue decrease(P <0.05), but the expression of OPG in in bone increased (P <0.01), and trabecular bone is close to thenormal bone marrow cavity, arrayed in the rules, the size is close to the normal (4)Adiponectin waspositively correlated with24hours urinary protein quality and blood calcium, alkaline phosphatase (P<0.05); while OPG was negatively correlated with blood calcium, alkaline phosphatase (P <0.01); AdipoR1was negatively correlated with OPG (P <0.01).Conclusions:1.The increased of adiponectin, AdipoR1in DN rats suggestted that there is osteoporosis.2.The expression of adiponectin,AdipoR1was significantly negatively correlated with OPG,suggesting that AdipoR1can induce the expression of OPG, and promote the occurrence of DO.3.Valproic acid can reduce the expression of adiponectin, AdipoR1, increase OPG, improveosteoporosis.