Dissertation > Medicine, health > Chinese Medicine > Of Pharmacy > Pharmacology

The Effect of Resveratrol on Preventing Steroid-Associated Osteonecrosis in Rabbits

Author DiJiLiang
Tutor WengXiSheng
School Beijing Union Medical College
Course Surgery
Keywords Osteonecrosis of the femoral head Osteonecrosis Resveratrol Dynamic MRI
CLC R285
Type PhD thesis
Year 2011
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Background and Objective: femoral head necrosis is a common clinical refractory diseases. Anticoagulant, lipid-lowering, increased osteoblast promote fibrinolysis is only one aspect of the femoral head necrosis in the pathogenesis, the treatment effect is not exact, more complications, and femoral head necrosis occurred before treatment can only delay the development of the course, does not make the disease reversed, and therefore the prevention of femoral head necrosis more meaningful. Resveratrol is a polyphenolic compounds with antioxidant, improve lipid metabolism and vascular endothelial function, and regulation of inflammatory cytokines and inhibit platelet aggregation and adhesion, which in the femoral head necrosis play an important role in the pathogenesis and, therefore, we have adopted Resveratrol rabbit steroid-induced osteonecrosis model intervention clear whether resveratrol to reduce the incidence of bone necrosis and explore its mechanism. Methods: 72 New Zealand white rabbits were randomly divided into four groups. Resveratrol prevention group (Pro group): 30 intravenous LPS (lipopolysaccharide endotoxin, 10μg/kg) and MPS (methyl prednisolone 20mg/kg), each injection interval 24h. LPS injection at the beginning of the day by intraperitoneal injection the resveratrol 4mg/kg/d, a total of two weeks. Model group, bone necrosis (AVN group): 30, with the Pro group intravenous injection of the same point in time the same amount of LPS and MPS intraperitoneal injection of the same amount of diluted alcohol, a total of two weeks. Resveratrol control group (Res group): 6, saline intravenous injection of the same amount with the same point in time Pro group were intraperitoneally injected with resveratrol 4mg/kg/d of 2 weeks. Blank control group (Con group): a total of six, with the same point in time Pro group intravenous injection of the same amount of saline diluted alcohol daily intraperitoneal injection of the same amount, a total of two weeks. Intravenous MPS 2 weeks and 3 months after the animals were sacrificed and specimens from bilateral femur and humerus specimens. Measured by ELISA at different time points of plasma tissue plasminogen activator (t-PA), plasminogen activator inhibitor -1 (of PAI-I), thrombomodulin (TM) and vascular endothelial growth factor (VEGF) level. Dynamic contrast-enhanced MRI to observe the different times of the femoral head perfusion. HE staining and immunohistochemistry to assess the incidence of osteonecrosis, tissue factor (TF) and VEGF expression. Results: 2 weeks osteonecrosis osteonecrosis model group was 80.0%, 43.8% the resveratrol prevention group, a significant difference (P = 0.043) between the two groups. 3 months, bone necrosis rate of the two groups were 50% and 36.4%, not statistically significant. Resveratrol control group and blank control group without bone necrosis occurred. MPS injection one week, two weeks and four weeks osteonecrosis model plasma TM and VEGF concentration was significantly higher than that resveratrol prevention group, but no significant difference between the two groups at 3 months. Wavy change of the t-PA and PAI-1 concentration of osteonecrosis model group and resveratrol prevention group, no significant difference between the two groups. Osteonecrosis model group ME significantly lower MPS injection one week, two weeks significantly increased, decreased 3 months resveratrol prevention group ME did not change significantly. Osteonecrosis model group TF and VEGF expression () or strongly positive (), weakly positive () or positive () resveratrol prevention group TF and VEGF expression. Conclusion: Transvenous single low dose endotoxin and high-dose methylprednisolone can be successfully induced to a rabbit hormone osteonecrosis model. Dynamic contrast-enhanced MRI can effectively judge the femoral head perfusion circumstances, consistent with the pathology of a reliable method for the early diagnosis of osteonecrosis. Resveratrol through a variety of mechanisms to improve the local blood supply of bone tissue, reduce the incidence of bone necrosis.

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