摘要
目的：通过观察桃红四物汤对激素性股骨头缺血性坏死碱性成纤维细胞生长因子(basic fibroblast growth factor bFGF)表达的影响，同时对比研究桃红四物汤对激素性股骨头缺血性坏死模型兔股骨头局部微血管密度和血液流变学的影响，进一步阐明活血化瘀法对激素性股骨头缺血性坏死的防治机理，为该方法的临床推广应用提供理论依据。
方法：60只健康成年新西兰大白兔，首先随机分为两组：正常组6只和实验组54只，实验组每周2次臀肌注射醋酸氢化泼尼松7.5mg／kg，经6周诱导出激素性股骨头缺血性坏死的早期模型；正常组每周2次臀肌注射同等剂量的生理盐水。6周后处死正常组6只和实验组6只，进行电镜观察，确定造模成功；将剩余实验动物随机分为中药治疗组和激素对照组：中药治疗组以桃红四物汤7ml／kg治疗，一日一次，激素对照组以生理盐水7ml／kg治疗，一日一次。并分别于治疗后第1、2、4周全部处死取材。进行组织病理观察、血液流变学、血清bFGF含量和股骨头局部微血管密度的检测。
结果：①电镜观察：实验组骨细胞数量减少，退变固缩或出现脂滴，成骨细胞减少，髓内脂肪细胞增大，正常组骨细胞富含粗面内质网，多聚核糖体多，线粒体发达，嵴结构清晰，核异染色质丰富，核仁可见。②组织病理学观察：激素对照组空缺骨陷窝数明显增多，骨小梁稀疏，髓腔脂肪细胞增大、增多；中药治疗组空缺骨陷窝数减少，骨小梁增多、增密。③血液流变学检测：激素对照组全血高切和低切粘度、血浆粘度、红细胞压积、纤维蛋白原含量等明显高于中药治疗组，并且，随着中药治疗时间的延长，中药治疗组血液流变学趋于正常，与激素对照组的差异更明显。④放射免疫检测血清bFGF的表达：中药治疗组bFGF的表达增强，与激素对照组相比有明显差异(p＜0.01)。⑤免疫组化检测股骨头局部血管密度的改变：中药治疗组股骨头局部血管密度逐渐增高，激素对照组股骨头局部微血管密度较中药治疗组明显减低。
结论：短期内大剂量使用激素，可以引起股骨头缺血性坏死，实验动物股骨头局部骨组织、骨细胞发生异常改变，血液流变学异常。桃红四物汤的使用可使激素性股骨头缺血性坏死模型兔bFGF的表达增强，从而可以有效促进微血管的再生，增加局部微血管密度；同时，桃红四物汤可明显纠正激素性股骨头缺血性坏死模型动物血液流变学异常，降低血液粘稠度，改善局部微循环障碍状态，促进激素性股骨头缺血性坏死的修复，这可能是活血化瘀法防治该病的机理之一。
Purpose: To investigate the effect on basic fibroblast growth factor、microvessel density and hemorheology of glucocorticoid-induced avascularnecrosis of femoral head in rabbits by treatment of tap hong si wu decoction. Tointerpret the mechanism of the effect on glucocorticoid-induced avascularnecrosis of femoral head by activating blood circulation, and offer a effectivemethod to clinical.
Method: 60 rabbits were randomly divided into 2 groups: 6 rabbits were in commongroup and 54 rabbits were in experimental group, the rabbits in common groupwere as normal control; the rabbits in experimental group were administered withhydroxyprednisone through gluteus injection (twice a week) for 6 weeks as control: there were 6 rabbits were killed in each group after 6 weeks, to be assure thatthe model were succed. All surplus rabbits were divided into healing group andcontrol group: the healing group were administrated with tap hong si wu decoction7ml/kg per day, the control group were administrated with sodium chloride 7ml/kgper day. then, after 1、2 and 4 weeks, killed the animal, and detected all indexes.
Results:①the result electron microscope showed: in the experiment group, bonecell decreased, cataplasised and pyknosised, lipid droplet emerged, the numberof osteoblast decreased, adipocytes in the camera pulpi accreted, bone cells inthe common group contained large number of rough endoplasmic reticulum andpolysome, bioblast becameprosperous, the architecture of the crista was lampros, kernel heterochromatin were plentiful, nucleolus could be seen.②histomorphologic measurements showed that empty lacuna increased and trabeculaof bone decreased more significantly in control groups and than those in healing group and the medullary cavity lipocytes in control group showed larger sizeand more amount than those in healing group.③whole blood viscosity, plasmaviscosity and fibrin in control groups increased significantly compared withthose in healing groups.④the expression of bFGF in serum measured byradioimmunity reinforced significantly in healing groups compared with controlgroups.⑤microvessel density(MVD) detected by immunohistochemistry: the MVD offemoral head in healing groups increased day by day, the MVD of femoral headin control groups degraded significantly compared with healing groups.
Conclusion: The administration of large dose glucocorticoid can induced avacularnecrosis of femoral head. the bone tissue and the bone cell of the femoral headand the hemorheology were changed abnormality, the condition could be improvedand the expression of bFGF could be reinforced by tap hong si wu decoction, atthe same time, it facilited the regeneration of capillary vessel and improvedthe condition of microcirculation, maybe that was one reason why tap hong si wudecoction effect on glucocorticoid-induced avacular necrosis of femoral head.
引文
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