| [Objective] The close relationship between Large quantity application of glucocorticoid and alcoholism and ANFH have got the approbation by large scholars,which make up 2/3 of totally ANFH cases. But pathogenesis of ANFH by glucocorticoid and is still not clear. In the last few years, the theory of capillaries hurts and intravascular coagulation is caused more and more attention. For this reason, to produce animal model of ANFH with alcohol, glucocorticoid, and horse serum added glucocorticoid. To contrast their differences in invasional time, pathological region and extent, especially to investigate the role of vasculitis and intravascular coagulation to induce ANFH. In addition, to evaluate the feasibility of laboratary symbols using in prethrombotic state and radioimmunoscintigraphy with nuclide labled monoclonal antibody against human fibrin in early diagnosis of ANFH. It would lay a foundation and provide the theory and experiment data for prophylaxis and therapeutics for ANFH.[Methods]Eighty adult Japanese white rabbits were chosen and randomly divided into four groups. Group I were administered with the strong distilledspirit containing 50%(v/v) of alcohol at dosage of 8ml .kg~-1 .d~-1. Group II were given intramuscular injection of methylprednisolone at dose 10mg.kg~-1 .d~-1 for 7 days. Then, the animal received prednisolone at dose 2.5mg.kg~-1 .d~-1 mixed with a small quantity of food until the end of the study. Group III were given intravascular injection of horse serum at dose 10ml.kg~-1 at 14 days intervals. Two weeks after the end of the immunization, the rabbits were received glucocorticoid according to group II. Group IV were used as controls. The animals in four groups were sacrificed in batches 1, 3 and 6 months after the procedures .The hepatic function, blood fat and serum cortisols were measured. The changes of histology in the hepar and femoral head were observed by means of HE staining, Sudan staining, microthrombus staining. In addition, activated partial thromboplastin time, prothrombin time , fibrinogen and blood viscosity was measured. Endothelins-I were examined by means of radioimmunoassay. Antithrombin-III and D-dimer were examined by means of immunoturbidimetry. Radioimmunoscintigraphy with 131I labled monoclonal antibody against human fibrin detect thrombus in the femeral head.[Results] l.The changes of serology: Three experiment group all showed the obvious hepatic function lesion, in which the first group administered with alcohol changed the most seriously. GGT (6.20 + 0.34 u.L"1) in the third month, AST (67.94 + 4.07 u.L"1) and ALT (79.93+ 7.24U.L"1) in the sixth month increased remarkbly with controls (3.72±0.22, 44.77±3.82, 52.95 + 3.97) respectively (PO.05) . Blood fat also showed high in 3 experiment group compared with controls, in which group III changes the most seriously.TG in third and sixth month was ( 2.63 ± 0.33mmol . L"1 , 6.56 ± O^lmmol.L"1) respectively, which increased remarkably compared with controls (l.OS + O^mmol.L"1, 1.33±0.25mmol.L"') (P<0.05) . CHO was remarkbly differenc between group III (2.83 ± 0.36mmol. L'1) and controls (1.65 + 0.23mmol. L"1) (p<0.05). The changes of serum cortisols in group I was 7.48 times than controls.2.The changes of Histology: (l)The changes of hepar: In three month, hepatocyte was covered with inequality lipid droplet and focal or sheet necrosis of hepatocyte were appeared in the group I. Other experimental group only showed fatty liver and point necrosis. (2)The changes of femoral head. Pathologic bone changes were classified into three grades. Grade 0 represented no pathologic changes and intact trabeculae and bone marrow. Grade 1 represented marrow necrosis without trabecular necrosis; bone marrow cells showed evidence of cytolysis, karyolysis,and adipocytes showed loss of nuclei and loss of distinct cell borders. Grade 2 consisted of ON with necrosis of bone marrow and trabeculae, where empty lacunae of osteocytes were observed in addition to the findings of Grade 1. In the first month, all specimens in AIG showed only Grade 0 changes. In the third month, two of four rabbits (50% ) showed Grade 1 changs and two of four rabbits (50% ) showed Grade 0 changs. In the sixth month, two of four rabbits (50% ) showed Grade 1 changs and one of four rabbits (25% ) showed Grade 2 changs. While one of five rabbits (20% ) in GIG showed Grade 1 changs in the first month, others specimens showed only Grade 0 changes. In the third month, three of five rabbits (60% ) showed Grade 1changs and two of five rabbits (40% ) showed Grade 0 changs. In the sixth month, three of five rabbits (60% ) showed Grade 1 changs and one of five rabbits (20% ) showed Grade 2 changs. In the first month, three of five rabbits (60% ) in SGIG showed Grade 1 changs, others specimens showed only Grade 0 changes. In the third month, two of five rabbits (40% ) showed Grade 1 changs and two of five rabbits(40% )showed Grade 2 changs. In the sixth month, two of five rabbits (40% ) showed Grade 1 changs and three of five rabbits (60% ) showed Grade 2 changs. The control group at various times was not observed abnormality in trabecular and marrow.Damage of endometrium, degeneration of media membrane,narrow of lumina even obstruction were observed. There were microthrombus in veins. Among them, the changs in group III was the most obvious.3.The changes of laboratary symbols using in prethrombotic state: In one month, the group showed that PT ( 8.03 ±0.47Sec) and APTT (30.83 ± 3.47Sec) began to decrease remarkably compared with controls (9.14 + 0.38Sec,36.14±3.38Sec) respectively (p<0.05) ; FIB (3.15+0.40^) and BV at high shear (4.21±0.26mpa.s) and low shear (9.49±1.49mpa.s) began to increase remarkably compared with controls (2.32 ± O^g-L"1,3.83 ±0.26mpa.s, 8.14 + 0.63 mpa.s) respectively (p<0.05) . AT-III (61.44+ 5.05mg.L"') was lower than controls (112.92+9.04mg.L/1) (p<0.01); ET-I (47.84+ U^pg-L"1) and D-dimer (0.53+0.19ug.ml"1) began to rise compared with controls (37.32+4.12pg-L"!, 0.43 + 0.1 lug .ml'1) respectively.4.Radioimmunoscintigraphy with 131I-SZ-63: In the third month, the group III showed the radioactivity uptake increasing remarkedly in both endsof the femur, especially in the femoral head. No abnormal signs were observed in other groups. The radioactivity ratios of femoral head to trunk in the group IIL group IL group I and controls were 2.16 ± 0.35 ^ 1.78 ± 0.3 K 1.68 + 0.29 and 1.57 ±0.12 respectively. There was statistical difference between the group III and the controls (P<0.01) . In the sixth month, the group II also showed the radioactivity uptake increasing slightly. [Conclusion] 1.Alcoholism and glucocorsticoid can both cause obvious hepatic lesion and disorder of blood fat, the pathological changes of the femoral head are same in some way. Furthermore, the former can increase the secretion of endogenous glucocorticoid, which may hint us that the disorder of blood fat may play a key role and the two have common in pathogenesis of ANFH.2. The incidence of ANFH in AIG was 50% in the third month and 75% in the sixth month respectively.3. The incidence of ANFH in GIG was 60% in the third month and 80% in the sixth month respectively.4. The incidence of ANFH in SGIG was 80% in the third month and 100% in the sixth month respectively5.Horse serum added glucocorticoid can induce typical ANFH. The disorder of blood fat,Vasculitis and intravascular coagulation were obvious, which hint us that disorder of blood fat and microvascular pathologic changs play an important role in the development of ANFH.6.Laboratary symbols using in prethrombotic state and radioimmunoscintigraphy with 131I-SZ-63 may provide a great potential inearly diagnosis and screening high risk group of ANFH.7. The occurrence of ANFH has a close relation with disorder of blood fat and PTS. It implied that the patients to drink arge quantity alcohol and use the glucoticoid or there is avasculitis should periodically check laboratary symbols using in prethrombotic state in order to early discovers and prevent the occurrence of ANFH. |
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