链脲佐菌素型糖尿病模型大鼠股骨头坏死的血脂、凝血代谢及组织病理学变化

Changes of serum lipid,coagulation metabolism and histopathology in femoral head necrosis of rat diabetic models induced by streptozotocin

背景:糖尿病性股骨头坏死的病理机制和病变特征至今尚未阐明。有研究证实,骨坏死与低纤溶状态有关,高脂血症是引起股骨头缺血性坏死的重要诱因。目的:拟观察糖尿病股骨头缺血性坏死模型大鼠的血脂、凝血代谢及组织病理学变化。设计、时间及地点:随机对照动物实验,于2006-04/2007-10在西安交通大学医学院第二附属医院骨科教研室及西安交通大学医学院病理教研室完成。材料:选用12周龄SD大鼠100只,适应性喂养2周后,精确称重,按性别抽取24只(雌雄各半)作为空白对照组,其余76只行速发型糖尿病大鼠模型制备。方法:模型组大鼠将60mg/kg链脲佐菌素腹腔快速推入,建立速发型糖尿病大鼠模型,使动物进食及饮水时双后腿负重,模拟人类髋关节生理状态。对照组24只给予腹腔针刺,不注入任何液体。主要观察指标:两组大鼠分别于造模成功后第4,8,12,18周麻醉后分批处死,对照组每次随机处死6只,模型组每次处死18只,进行大体形态、组织病理学、血脂及凝血指标检测。结果:造模成功后模型组大鼠日渐消瘦,食欲旺盛,饮水量增加,体质量逐渐下降。模型组大鼠电镜下均可见骨小梁表面成骨细胞减少,活性降低;光镜下观察,与同期对照组比较,自造模第4周后空骨陷窝计数显著增加(P<0.01)。与同期对照组相比,模型组大鼠造模后第8,12,18周活化部分凝血活酶时间、凝血酶原时间及凝血酶时间显著缩短(P<0.05～0.01),纤维蛋白原水平显著升高(P<0.05～0.01),血清总胆固醇、三酰甘油浓度显著升高(P<0.01),高密度脂蛋白显著降低(P<0.05～0.01)。结论:糖尿病可引起长期骨质疏松、高脂血症、血液高凝状态,这些因素共同作用下将会最终导致糖尿病股骨头缺血性坏死的发生。

BACKGROUND： The pathological mechanism and pathologic character of femoral head necrosis induced by diabetes mellitus remains unclear, previous studies proved that osteonecrosis related to hypercoagulative state, hyperlipemia is one of the important inducements to femoral head necrosis. OBJECTIVE： To study the serum lipid and blood clotting and histopathology changes in femoral head necrosis of diabetic rat models DESIGN, TIME AND SETTING： Randomized controlled animal study was performed at the Department of Orthopaedics, and Department of Pathology, Second Affiliated Hospital of School of Medicine, Xi＇an Jiaotong University between April 2006 to October 2007. MATERIALS： After two week adaptive feed, twenty-four rats of 100 anmials with 12-weeks-old, half males and females, were selected as the control group, other animals were prepared for diabetic models. METHODS： Rats in the model group were given intraperitoneal injection. 60 mg/kg streptozotocin, simulate the physiological state of human hip joints, and rats in the control group were only performed intraperitoneal acupuncture. MAIN OUTCOME MEASURES： After model preparation, 6 rats in the control group and 18 in the model group were sacrificed and examined gross morphology, histopathology, serum lipid and blood clotting changes at 4, 8, 12, 18 weeks, respectively. RESULTS： Rats in the model group were appeared diabetic symptoms such as emaciation, honey stomach, and drank more water. Under electron microscope, few of osteoblasts with low activity could be found in the model group. Compared with the control group, the number of empty osteocyte lacuna in the model group was significantly increased at 4 weeks （P 〈 0.01）. The activated partial thromboplastin time, plasma thromboplastin, thrombin time, fibrinogen were more notably shortened at 8, 12, 18 weeks （P 〈 0.05-0.01）, the fibrinogen level was obvious increased （P 〈 0.05-0.01）, contents of total cholesterol, triglyceride were significantly increased （P 〈 0.01）, but the high density lipoprotein was lower （P 〈 0.05～0.01）. CONCLUSION： Diabetes can result in osteoporosis, hyperlipemia, and high blood coagulation states, eventually induce femoral head necrosis.