内源糖皮质激素对酒精性股骨坏死凋亡细胞p53和Bcl-2影响

Effects of Endogenous Glucocorticoid(GC) on the Expression of p53 and Bcl-2 Proteins in Osteocyte Apoptosis in Avascular Necrosis of the Femoral Head Induced by Alcoholism

探讨内源糖皮质激素对酒精性股骨坏死凋亡细胞p53和Bcl-2蛋白的影响。选用90只家兔,随机分为3组。采用给予灌胃法实验组家兔含乙醇50%的烈性白酒8mL/kg·d,药物干预组等量白酒加氨鲁米特25mg/kg·d,对照组等量生理盐水,1～6个月。原位杂交检测GCR mRNA表达,TUNEL法检测骨细胞凋亡。结果表明,实验组和干预组股骨头骨细胞分别于2～3个月时GCR mRNA表达开始减弱;对照组为中等表达。实验组2个月时骨细胞凋亡数明显高于干预组和对照组,但干预组与对照组之间差异无显著性。第3、6个月时实验组、干预组、对照组之间差异均有显著性。实验组Bcl-2蛋白表达第2个月与对照组之间差异有显著性,且与骨细胞凋亡数成明显的负相关性;实验组p53蛋白表达阳性数第2、3、6个月均明显高于对照组,且与骨细胞凋亡数成明显的正相关性。酒精性股骨头缺血坏死骨细胞存在明显的凋亡现象,且受p53蛋白上调和Bcl-2蛋白下调影响,二者共同调节骨细胞凋亡。

The effects of endogenous glucocorticoid （EGC） on the expression of p53 and Bc1-2 proteins in osteocyte apoptosis in avascular necrosis of the femoral head induced by alcoholism were investigated. 90 rabbits were divided into three groups randomly. The experimental group were administered with liquor （50 % alcohol content） at dosage of 8 mL/kg·d,the intervention group were given aminoglutethimide 25 mL/kg·d, and the control group were given isodose NS only by pouring into stomach with tube. The levels of serum EGC were detected from 1 to 6 months. The osteocytes apoptosis was measured by means of TUNEL, and the expression of p53 and Bc1-2 proteins by imunohistochemistry. The results showed that the numbers of apoptosis osteocytes in the experimental group were evidently higher than that of the intervention group and the control group in the second month （no significant difference between the intervention group and the control group） and there was significant difference among the three groups in the third and in the sixth month. In the second month, the amount of Bc1-2 protein expression of osteocytes in the experimental group decreased （negative relativity with osteocytes apoptosis）, and the level of p53 protein of osteocytes were increased （positive relativity with osteocytes apoptosis） than that in other groups. In the third and the sixth month, the amount of Bc1-2 protein expression of osteo- cytes in the experimental group significantly were decreased, the expression of p53 protein of osteocytes were remarkably increased than that in other groups. It was concluded that EGC was an important factor in the apoptosis in osteocytes of ANFH by alcoholism.