Comparative Study Of Different Therapeutic Methods Prevent The Occurrence Of Steroid - Induced Necrosis Of The Femoral Head

Background: The incidence of steroid-induced avascular necrosis of femoral head (SANFH) shows a tendency of increasing year by year. At present, there are many methods to treat SANFH with traditional Chinese medicine and/or western medicine, but the therapeutic results are not satisfactory. Many patients with SANFH have to take artificial hip replacements because of the collapse of femoral head and disfunction of the hip joint. Therefore, it is important and essential to take effective measure to prevent SANFH. Previous clinical research shows that 'comorbidity of phlegm and silt' and 'renal deficiency' are two key pathogenesises of SANFH. Whether 'invigorating spleen to remove phlem & promoting blood circulation to remove meridian obstruction' and 'invigorate the kidney & promoting blood circulation to remove meridian obstruction' can prevent SANFH remains unknow.Objective: To investigate the pathogenesis of SANFH in chickens. To evaluate and compare the effects of the methods of 'invigorating spleen to remove phlem & promoting blood circulation to remove meridian obstruction' and 'invigorate the kidney & promoting blood circulation to remove meridian obstruction' preventing SANFH in chickens.Method: 80 chickens were randomly assigned to 5 groups (n =16) : Blank control group, model group, Lovastatin (10mg/d), Huogu recipeⅠgroup(with therapeutics of invigorating spleen to remove phlem, 6ml/kg/d), Huogu recipeⅡ(with the effect of warming kidney for duresis, 9ml/kg/d). All chickens were injected intramuscularly with Meticortene Soluble once a week for 16 weeks but that in blank control group. The route of delivery was oral administration. Sera were obtained respectively from the chickens on 4,6,8,10 and 12 weeks to detect hematic indexes. Bilateral femoral heads were dissected. Paraffin tissue sections were prepared to detect histopathologic change with hematoxylin and eosin, or mason. The production and expression of TGFβ1, BMP2, Smad4, Smad7 and VEGF in femoral bone with were detected by immunohistochemistry method, and OPG, RANKL by in situ hybridization (ISH) method.Results:Histological analysis showes that Huogu recipeⅠand Huogu recipeⅡcan promote osteogenesis and repair osteonecrosis , increase blood circulation of bone marrow, and inhibited pimelosis of bone marrow.CHO, TG, and LDL increased and HDL decreases in model group compared with normal group.Plasma viscosity, and blood viscosity increased in model group compared to normal group. Huogu recipeⅠand Huogu recipeⅡcan obviously decrease plasma viscosity and blood viscosity, especially on 4 and 8 weeks in Huogu recipeⅠgroup and on 12 and 16 week in Huogu recipeⅡgroup. Lovastatin can also improve blood viscosity.FIB decreased in blood plasm, and APTT decreased in model group compared to normal group. Huogu recipeⅠand Huogu recipeⅡcan obviously ameliorate the condition of blood clotting such as FIB, TT and APTT, especially on week 8 for Huogu recipeⅠand on week 16 for Huogu recipeⅡ. Lovastatin can also improve the condition of blood clotting, but not well as traditional Chinese medicine.PLG and AT-Ⅲelevated on week 16 in model group compared to normal group. Huogu recipeⅠcan significantly decreased PLG and t-PA.Immunohistochemical analysis indicated that TGFβ1,BMP2,VEGF, Smad4 are low expressed and Smad7 is high expressed in femoral head of model group compared with normal group. Huogu recipeⅠand Huogu recipeⅡcan predominantly interfered with the production of TGFβ1, BMP2, VEGF and Smad4．ISH analysis indicated that Huogu recipeⅠand Huogu recipeⅡeffectively upregulated OPG mRNA and downregulated RANKL mRNA in femoral head. Conclusions: Steroid can induce SANFH in chickens. The pathogenesis of SANFH is correlated with fat metabolic disturbance, functional disorder of blood clotting and plasminogen, and the inhibition the expression of TGFβ1, BMP2, Smad4, OPG mRNA and augmentation the expression of Smad7 and RANKL mRNA. Huogu recipeⅠand Huogu recipeⅡboth can prevent SANFH in chickens by different mechanisms.