| ObjectiveDiabetes is seriously endangering people's health, and the disease is currently following heart disease and cancer. With the advent of an aging society, the incidence of diabetes has increased over year by year. Diabetes osteoporosis(DOP) are secondary OP. DOP is one of the most common complications of diabetes mellitus(DM), which is often along with the series of pathological changes.OLETF rats are a spontaneous type 2 diabetic model. LETO rats and OLETF rats which were taken rosiglitazone, were enrolled as controls, respectively. Bone histomorphometric, bone mineral density (BMD) and the expression of bone morphogenetic protein-2 (BMP-2) and Bcl-xL of osteoblast were observed to seek the possible mechanism for bone metabolic disturbance.MethodsBlood glucose was determined by oral glucose tolerance test (OGTT) for 20 male OLETF rats. The diabetes was confirmed with blood glucose peak level>16.7 mmol/L and blood glucose level>11.1 mmol/L taken glucose 120 minutes later. After 30 weeks,12 T2DM OLETF rats were randomly divided into diabetes mellitus control (DM) group and rosiglitazone (RGZ) group (n=6 per group). Eight male LETO rats were used as a normal control (NC) group. DM group and NC group were watered intragastrically for 12 weeks. RGZ group was taken the rosiglitazone (3mg/kg-d) intragastrically for 12 weeks.After the rats were sacrificed, their left and right femurs were severed completely, and peeled soft tissue carefully. The left femurs covered with isotonic saline gauze were in -20℃refrigerator for measuring BMD, bone collagen and the ratio of ash weight to dry weight of femur. The right femurs within 10% formaldehyde solution were in 4℃refrigerator for observating the expression of BMP-2 and Bcl-xL of osteoblast.BMD at the femur was assessed by dual energy X-ray absorption (DEXA). Make right side of the femur into microtome section after the process of immobility and decalcification. Observe their pathological change by using optical microscope and detect the expression of BMP-2, Bcl-xL in osteoblast through making use of immunohistochemistry. All results were performed with analysis software for multimedia pathological image.Results1. Obervation of the general conditions of ratsOLETF rats drank much, ate much, had polyuria and felt significantly bleak, and were dull coat. The spirit of OLETF rats was worse than LETO rats. LETO rats' drinking and eating were normal.2. Comparison of BMD in femurs among three groups of ratsCompared with the DM group [(0.198±0.011) g/cm2], NC group [(0.220±0.012) g/cm2] had higher BMD (P<0.01), and RGZ group [(0.172±0.012) g/cm2] had significantly lower (P<0.01).3. Comparison of the ratio of ash weight to dry weight in femur among three groups of ratsCompared with the DM group (0.521±0.012), NC group (0.538±0.018) had higher ratio of ash weight to dry weight of femur (P<0.05), and RGZ group (0.492±0.011) had significantly lower (P<0.01).4. Comparison of the decalcification condition in femurs among three groups of ratsCompared with the DM group, NC group had significantly longer decalcification time of femurs and (bone weight - bone weight after decalcification)/bone weight (P<0.01); RGZ group had lower (P<0.05).5. Comparison of the empty osteocyte lacunae ratios, the amount of osteoblast (OB) and osteoclast (OC) in femur among three groups of ratsCompared with the DM group, NC group had higher amount of OB (P<0.01), and had lower empty osteocyte lacunae ratios and amount of OC (P<0.05 or P<0.01); RGZ group had lower amount of OB (P<0.05), and had higher empty osteocyte lacunae ratios and amount of OC(P<0.01).6. Comparison of collagen in femur among three groups of ratsCompared with the DM group[(185.60±19.38)mg/g], NC group[(243.27±22.19)mg/g] had higher content of collagen(P<0.01); RGZ group[(158.81±17.65)mg/g] had lower(P<0.05). 7. Comparison of the expression of Bcl-xL in osteoblasts among three groups of ratsCompared with the DM group(84.83±10.82), NC group(69.13±11.56) had higher the intensity of positive expression of Bcl-xL(P<0.05); RGZ group(110.17±15.33) had lower(P<0.01).8. Comparison of the expression of BMP-2 in osteoblast among three groups of ratsCompared with the DM group (0.4886±0.0398), NC group (0.5571±0.0402) had higher intensity of positive expression of BMP-2(P<0.01); RGZ group(0.424 7±0.0321) had lower(P<0.01).Conclusions1. The rat model is obesity, and can be the ideal animal model for study on abnormality of bone metabolism under type 2 diabetes.2. The diabetic rats have decreased BMD and bone mass. The dysfunction of osteoblasts might be the major mechanism for bone metabolic disturbance under diabetic status, in which osteoclasts may involve.3. The bone collagen of T2DM's rats is different from that of rats without T2DM. The metabolism of bone collagen is abnormal and the structures of bone collagen are confused in T2DM's rats. The former presents that the content and synthesis of bone collagen is reduced. The latter presents that the continuity of bone collagen is bad and the alinement of it is untidy.4. Rosiglitazone increases the damage effect on the femurs in OLETF rats.
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