小干扰RNA预防兔激素性股骨头坏死的组织病理学观察  

The histopathological observation： prevention of steroid - induced osteonecrosis of the femoral head of rabbits by small interfering RNA in vivo

作　　者：马源[1] 张善锋[2] 刘鸣[1] 李劲峰[1] 王义生[1] 李月白[2] 赵国强[3] 

机构地区：[1]郑州大学第一附属医院骨科河南省高等学校临床医学重点学科开放实验室,450052 [2]郑州大学基础医学院生物化学与分子生物学系,450001 [3]郑州大学基础医学院微生物与免疫学系,450001

出　　处：《中华实验外科杂志》2016年第7期1747-1749,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金（81071520）

摘　　要：目的观察靶向过氧化物酶体增殖物激活受体γ（PPARγ）基因小干扰RNA预防兔激素性股骨头坏死（ONFH）的组织病理学变化。方法将48只兔随机分为4组。股骨头坏死模型组（M）：给予地塞米松20mg／kg，连续肌肉注射3d。干扰组（S）：同样给予地塞米松，并于实验1、3、6周给予siRNA腺病毒滴液25山注入一侧股骨头内。无关序列组（Con）：同样给予地塞米松，注入兔股骨头内无关序列siRNA病毒滴液。正常组（N）：无特殊处理。实验第4、8周末分批处死兔，观察兔股骨头组织病理学改变。结果实验8周时，干扰组、模型组、无关序列组、正常组中，最大脂肪细胞平均直径分别为（41．21±2．33）、（49．61±1．13）、（49．22±2．18）、（40．94±2．09）μm；骨小梁面积分数分别为（40．93±1．96）、（31．51±4．26）、（30．79±1．85）、（41．64±2．34）％；空骨陷窝计数分别为（12．07±1．38）、（21．54±1．38）、（21．76±1．46）、（11．67±1．28）％。模型组和无关序列组中发生明显的早期ONFH组织病理学变化，股骨头软骨下骨区造血组织大大减少、骨髓坏死、脂肪细胞增殖肥大、平均直径明显增大、骨小梁变细稀疏或断裂、骨小梁面积分数明显降低、空骨陷窝显著增多。而正常组中无这些病理学改变（P〈0．05）。干扰组股骨头病理学改变较少，接近于正常组（P〉0．05），与模型组和无关序列组之间的差异均有统计学意义（P〈0．05）。模型组、无关序列组中ONFH发生率为83％、83％，干扰组、正常组中为33％、0％（P〈0．05）。结论靶向PPARγ基因小干扰RNA能够有效阻止激素导致兔ONFH的组织病理学改变，预防激素性ONFH的发生。Objective To observe the histopathological changes of small interfering RNA （siRNA） targeting on peroxisome proliferator activated receptor γ （PPARγ） preventing steroid - induced osteonecrosis in rabbits femoral head （ONFH） in vivo. Methods Forty - eight rabbits were randomly divided into four groups. In the model group （ group M）, dexamethasone 20 mg/kg was injected continuously for 3 days. In the interference group （group S） , dexamethasone was given the same as in the group M, and siRNA adenovirus drops （25 μl） were injected into one side femoral head at 1,3, and 6 week. In the irrelated sequence group （group Con）, dexamethasone was given the same at in the group M, and a vector carrying irrelative sequence was injected into one side femoral head at 1, 3, and 6 week. In the normal group （group N） , 2 ml normal saline was injected. Experimental animals were sacrificed at 4th and 8th week to observe the histopathological changes in rabbits femoral head. Results At 8th week of experiment, the data of histopathological changes in groups S, Con, M and N showed as follows ： the biggest adipocytes diameter was （41.21 ±2.33）, （49. 61 ± 1.13）, （49. 22±2. 18）, and （40. 94±2. 09）μm respectively. Bone trabecular area fraction was （40. 93 ± 1.96 ） % , （ 31.51 ± 4. 26 ） % , （ 30.79 ± 1.85 ） %, and （41.64 ± 2. 34） % respectively. The percentage of empty osteocyte lacunae was （ 12. 07 ± 1.38 ） %, （ 21.54 ± 1.38 ） % , （21.76 ± 1.46） % , and （ 11.67 ± 1, 28 ） % respectively. Obvious early pathological changes of ONFH were seen in the groups M and Con at bone area under cartilage, such as reduced hematopoietic tissue, bone marrow necrosis, adipocyte proliferation and hypertrophy, significantly increased average diameter, thin sparse or fracture of trabecular bone, decreased bone trabecular area fraction, and significantly increased empty bone lacunae. On the contrary, there were no histopathological changes of ONFH in the normal gro

关 键 词：小干扰RNA 激素 股骨头坏死 组织病理学 

分 类 号：R681.8[医药卫生—骨科学]