激素性股骨头坏死模型中凋亡相关因子的表达

背景：近年研究发现,激素性股骨头坏死模型中存在大量凋亡骨细胞,而Caspase-3 及Bcl-2 为调节细胞凋亡的两个重要因子。目的：观察Bcl-2和Caspase-3在激素性股骨头坏死大鼠模型中的表达及二者的相关性。方法：选取健康Wistar大鼠60只随机分为2组,实验组臀肌注射泼尼松龙12.5 mg/kg,每周2次,制备激素性股骨头坏死模型;对照组注射等量生理盐水。分别于给药后4,8,12周获取离体大鼠股骨头,采用苏木精-伊红染色观察骨组织形态学改变,免疫组织化学染色观察Bcl-2和Caspase-3蛋白的表达水平,并采用直线相关分析Bcl-2和Caspase-3的相关性。结果与结论：对照组及实验组股骨头外形均完整,软骨面平整、光滑。随着给药时间的延长,实验组大鼠股骨头内骨小梁逐渐变细,脂肪细胞增多,骨陷窝空虚率明显升高。免疫组织化学染色显示：与对照组比较,实验组大鼠股骨头Caspase-3表达明显增高(P < 0.01),且随给药时间的延长呈逐渐增高趋势;而Bcl-2的表达显著低于对照组(P < 0.01)。相关分析结果显示Bcl-2和Caspase-3在各组内的表达不具有相关性。提示激素可提高Caspase-3的表达促进骨细胞凋亡,降低Bcl-2的表达抑制抗凋亡作用,进而导致激素性股骨头坏死的发生和发展。

Apoptosis-related factors in a model of steroid-induced necrosis of the femoral head

BACKGROUND:Recent studies have shown that a large amount of apoptotic osteocytes in the model of steroid-induced necrosis of the femoral head. Caspase-3 and Bcl-2 are two important factors for regulation of cell apoptosis.OBJECTIVE:To observe Bcl-2 and Caspase-3 levels in a rat model of femoral head necrosis and their correlation.METHODS:Sixty healthy Wistar rats were randomly divided into two groups (n=30). Experimental group was treated with gluteal muscle injection of prednisolone 12.5 mg/kg, twice per week, for establishing a femoral head necrosis model; control group was injected with the same amount of normal saline. Rat femoral head was removed after 4, 8 and 12 weeks respectively. Bone tissue morphological changes were observed by hematoxylin-eosin staining and the protein expression levels of Bcl-2 and Caspase-3 were observed using immunohistochemical staining. Linear correlation analysis was performed for analysis of correlation between Bcl-2 and Caspase-3.RESULTS AND CONCLUSION:Femoral heads were complete in the experimental and control groups with smooth and flat cartilage surface. In the experimental group, the trabecular bone in the femoral head gradually became thinner, the number of adipose cells increased and percentage of empty lacunae significantly increased with the time of administration. Caspase-3 expression increased significantly in the experimental group compared with the control group (P < 0.01), trending to gradually increase with the time of administration. Conversely, the expression of Bcl-2 was lower in the experimental group than the control group (P < 0.01). The linear correlation analysis showed that there was no correlation between Bcl-2 and Caspase-3. These findings indicate that steroids can increase the expression of Caspase-3 promoting apoptosis of osteocytes and reduce the expression of Bcl-2 inhibiting anti-apoptotic role, which leads to the occurrence and development of steroid-induced necrosis of the femoral head.