高龄小鼠沉默信息调节因子1基因敲除后膝骨关节炎模型的建立

发布时间：2018-09-07 22:07

【摘要】：背景:国内外学者对骨关节炎的发病机制和治疗方法进行了大量的研究,近期发现沉默信息调节因子1(SIRT1)基因在骨关节炎的发病中有着重要的意义,但对其研究尚少,用于该基因研究的骨关节炎模型也鲜有报道。目的:建立特异性的高龄SIRT1基因敲除小鼠膝骨关节炎模型,以期为骨关节炎的研究提供便利条件。方法:采用随机对照分组的方法,将小鼠分为4组,即SIRT1~(+/+)小鼠假手术组(A组)、SIRT1~(+/+)小鼠骨关节炎模型组(B组)、SIRT1~(-/-)小鼠假手术组(C组)及SIRT1~(-/-)小鼠骨关节炎模型组(D组),每组6只。行单侧膝关节前交叉韧带横断加内侧半月板切除建立骨关节炎模型,荧光定量聚合酶链反应检测SIRT1基因敲除情况;苏木精-伊红染色、番红O-固绿双染色观察膝关节软骨形态结构改变,Mankin评分评价膝骨关节炎程度。结果与结论:SIRT1~(-/-)小鼠SIRT1 mRNA表达量明显低于SIRT1~(+/+)小鼠(P0.01),说明SIRT1基因敲除成功。染色结果显示,B、D两组膝关节软骨破坏明显,Mankin评分明显高于A、C两组(P0.01),并且SIRT1基因敲除后Mankin评分升高更明显(P0.05)。提示软骨组织特异性SIRT1基因敲除膝骨关节炎小鼠动物模型建立成功。
[Abstract]:Background: scholars at home and abroad have done a lot of research on the pathogenesis and treatment of osteoarthritis. Recently, it has been found that silencing information regulatory factor 1 (SIRT1) gene plays an important role in the pathogenesis of osteoarthritis, but little research has been done on it. Osteoarthritis models used in the gene study are also rarely reported. Objective: to establish a specific SIRT1 gene knockout mouse knee osteoarthritis model in order to provide a convenient condition for the study of osteoarthritis. Methods: the mice were randomly divided into 4 groups. The SIRT1~ (/) mouse sham-operated group (A group) and the SIRT1~ (-r-) mouse osteoarthritis model group (D group) were divided into two groups: the model group (group B) and the sham operation group (group C) and the group D (group D). The osteoarthritis model was established by unilateral anterior cruciate ligament transection and medial meniscus resection. SIRT1 gene knockout was detected by fluorescence quantitative polymerase chain reaction. Observation of articular cartilage morphologic changes and Mankin score to evaluate the degree of knee osteoarthritis. Results and conclusion the expression of SIRT1 mRNA in SIRT1 ~ (- / -) mice was significantly lower than that in SIRT1~ (/) mice (P0.01), which indicated that SIRT1 gene knockout was successful. The results of staining showed that the cartilage damage of knee joint in group B and D was significantly higher than that in group C (P0.01), and the Mankin score increased significantly after SIRT1 gene knockout (P0.05). The results suggest that the animal model of cartilage tissue specific SIRT1 knockout knee osteoarthritis was successfully established.
【作者单位】：北京大学深圳医院;
【基金】：国家自然科学基金面上项目(81272032) 深圳市卫人委资助项目(201302064) 深圳市科创委资助项目(JCY20130402114702130)~~
【分类号】：R-332;R684.3

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