【作者】 王明千；

【导师】 齐振熙；

【作者基本信息】 福建中医学院 ， 中医骨伤科学， 2005， 硕士

【摘要】 背景:随着全球人均酒精消费量逐年攀升,其相关性疾病日益增多,酒精性股骨头缺血性坏死（alcohol-induced avascular necrosis of femoral head.AIANFH）的临床病例呈现增多趋势,近年来,探讨AIANFH的发病机制已成为研究热点。 目的:通过动物实验研究AIANFH的发病机制,为临床寻找最佳治疗方案和疗效提供有力证据。 方法:健康成年SD大鼠120只,随机分为三组,每组40只。采用酒精灌胃法,实验组A给予45°白酒8ml·kg^-1·d^-1(含纯酒精约4g·kg^-1·d^-1)灌胃。实验组B给予45°白酒6ml·kg^-1·d^-1(含纯酒精约3g·kg^-1·d^-1)灌胃。对照组给予生理盐水灌胃。分别于8、16、24周处死取材,进行大体形态、组织病理学、透射电镜观察、脂质代谢、血液流变学、氧自由基、一氧化氮、核素扫描等指标检测。 结果: 1、大体观察:对照组全身状况是:大部分体重无明显变化,小部分有逐渐增加趋势,股骨头外观正常;实验组全身状况较差,大部分体重增长明显,呈肥胖趋势,股骨头软骨破坏,或静脉淤血,或股骨头坏死塌陷,实验组A最明显,实验组B次之。 2、组织病理学观察:对照组正常。第8、16周各组比较,差异无统计学意义（P>0.05）。第24周空缺骨陷窝计数:各组间均有明显差异（P<0.05或P<0.01）。实验组A股骨头骨细胞变性、坏死,空缺骨陷窝增多,骨小梁变细、断裂,结构紊乱。实验组B较实验组A轻。 3、电镜观察:对照组正常。第24周实验组A骨细胞坏死、退变,胞核固缩,或出现脂滴,数量减少,成骨细胞减少,髓内脂肪细胞增多、增大。实验组B较实验组A轻。 4、脂质代谢:第8、16周各组比较,差异无统计学意义（P>0.05）。第24周实验组A胆固醇、甘油三酯和低密度脂蛋白明显升高,高密度脂蛋白降低。各组间比较,差异有统计学意义（P<0.05或P<0.01）。 5、血液流变学:第8、16周各组比较,差异无统计学意义（P>0.05）。第24周实验组A全血低切粘度、全血高切粘度、血浆粘度、全血还原粘度、红细胞聚集指数均明显更多还原

【Abstract】 Background:The disease related to alcohol grows day by day with the increase of average consumption of alcohol,and the number of alcohol-induced avascular necrosis of femoral head (AIANFH) presents a growth trend,at present it’s a hotspot to probe into the pathogenesy of AIANFH.Purpose: To study the relationship between different doses of alcohol intake and femoral head avascular necrosis in rats,to establish an ideal and practical animal model which might investigate the pathogenesis of femoral head avascular necrosis.Method: 120 rats were randomly divided into 3 groups, each group consists of 40 rats. experimental group A(EG A) was administered the wine containing 45% of alcohol at dosage of 8ml.kg~-1 .d~-1(equal to 4g.kg~-1.d~-1), experimental group B(EG B) was administered the wine containing 45% of alcohol at dosage of 6ml.kg~-1.d~-1(equal to 3g.kg~-1.d~-1), and control group conducted the same amount of NS respectively. All animals were killed in 8 weeks, 16 weeks, 24 weeks respectively after the start of the procedure. Detected indexes as followed: the conditions of rats, the changes of histology in the femoral head,electron microscope analysis, the items of lipid metabolism, hemorheology, oxygenfree radical(OFR), endothelin(ET) and nitric oxide(NO), radioisotope scanning.Results: 1.The conditions of rats:the in control group was better than in other groups;most of the rats of the control group’s weight didn’t change,their shapes of femoral head were normal. In experimental groups(EG A and EG B), the weight increased slowly and the cartilage of the femoral head were destroyed,or there were stases of veins,or the femoral heads caved in.Pathological changes of EG A was more obvious than those of EG B.2.Histology:the contrlo group was normal;there was no difference between them after 8,16 weeks(p>0.05);there was significant difference between their quantities of empty osteocyte lacuna after 24 weeks(p<0.05 or p<0.01).In experimental groups, empty osteocyte lacuna increased and trabecula of bone decreased, ruptured. Pathological changes of EG A was more obvious than those of EG B.3.Electron microscope analysis:the control group was normal;osteocytes and osteoblasts in experimental groups decreased,nucleolus shrunk,and osteocytes had degeneration signs or fatty drips appeared in osteocytes, and intramedullary lipocytes became larger in experimental groups. Pathological changes of EG A was more obvious than that of EG B.4.Lipid metabolism: there was no difference between them after 8,16 weeks(p>0.05); TC,TG,LDL increased significantlyin EG A,HDL decreased significantly in EG A after 24 weeks;there was significant difference between EG A and the control group(p<0.05 or p<0.01).5.Hemodynamics:there was no difference between them after 8,16 weeks(p>0.05);whole blood viscosity(low-shear and high-shear), plasma viscosity and whole blood relative viscosity at low-shear rate;RBC aggregation index of EG A increased sigificantly in the 24th week;there was significant difference between EG A and the control groupafter 24 weeks(p<0.05 or p<0.01).6.Levels of MDA: there was no difference between EG A and the control group after 8,16 weeks(p>0.05).EG A’s Level of SOD decreased in the 24th week significantly,and there was significant difference between EG A and the control group(p<0.05).EG A’s level of MDA increased significantly,and there was significant difference between EG A and the control group(p<0.05);there was significant difference between EG B and the control(p<0.05).7.The level of serum NO: there was no difference between them after 8,16 weeks(p>0.05);the level of serum NO in EG A decreased after 24 weeks.There was significant difference between EG A and the control group(p<0.05);there was no difference between EG B and the control group(p>0.05).8.The level of plasma ET: there was no difference between them after 8,16 weeks(p>0.05);the level of plasma ET increased significantly.There was significant difference while each group was compared with another(p<0.05 or p<0.01).9.Radioisotope scanning:EG B and the control group were normal.The radioisotope of blood stream picture was sluggish in the femoral head of EG A after 24 weeks,and there was concentration phenomenon of blood pond radioisotope.There was concentration phenomenon of radioisotope in the femoral head of the whole body picture. Conclusion:1 .the high dose of alcohol intake can induce the disorder of lipid metabolism,and came into being hyperlipemiaJt’s because of the cumulative effect of fat embolism in bone,the high pressure in marrow,the hindering of the vein refluence and the accroching fatty degeneration in bone cell,et al,so the blood supply of femoral head was discontinued,and the necrosis formed.2. the high dose of alcohol intake can induce the change of hemorheology, its viscosity enhanced; it’s because of the blood stasis,the defilade of microcirculation,the present of thrombus, the blood supply of femoral head was discontinued,and the necrosis formed.3. the high dose of alcohol intake can induce the OFR metabolic disorder.Lipid over-oxidation accelerated the pathological changes of microvascular,aggravated the barrier of micrcirculation of the femoral head,accelerated AIANFH.4. the high dose of alcohol intake can induce plasma ET increased and serum NO decreased,which can induce the contraction of blood vessel. and the presentation of thrombus,then the blood supply of femoral head was discontinued,and the necrosis formed.5.the detection of ECT showed that the distribution of nuclide in blood film was retarded;the distribution of nuclide in blood pool film concentrated;the concentration of nuclide in femoral head can be found in femoral head image of all over the body.which is cue that there was blood stasis in bone, pathological tissue is presented in segment,or new bone formed.So ECT is significant to the early diagnosis of AIANFH.更多还原