富马酸二甲酯对大鼠椎间盘退变髓核中低氧诱导因子-1α表达和功能的影响

Experimental research on the effect ofdimethyl fumarate on the expression and function of hypoxia-inducible factor-1α on rat intervertebral disc degeneration

目的建立SD大鼠腰椎间盘退变模型采用测定低氧诱导因子-1α(HIF-1α)在大鼠模型腰椎间盘髓核中的表达情况及作用,探讨富马酸二甲酯(DMF)对其表达及功能的影响。方法对大鼠腰椎退变模型行磁共振成像(MRI)扫描后,取L4/L5节段髓核组织行蛋白多糖检测,石蜡包埋、切片后进行HIF-1α的免疫组化染色。结果 MRI结果显示模型对照组(B组)的椎间盘髓核存在明显的退变,T2加权相信号降低(P<0.05)。B组髓核中的HIF-1α呈强阳性,与另两组比较差异有统计学意义(P<0.05)。对全部的髓核组织的进行蛋白多糖含量的检测,可见对照组B组的蛋白多糖成分(2.06±0.04)ng·g^(-1),流失最为严重,富马酸二甲酯用药组(C组)(2.06±0.05)ng·g^(-1)相对较轻,正常对照组(A组)含量为(3.28±0.03)ng·g^(-1),三组比较差异有统计学意义(P<0.01)。结论 HIF-1α在退变的腰椎间盘组织中表达增高,其表达与腰椎的退变密切相关。富马酸二甲酯作为HIF-1α的抑制剂能降低HIF-1α的表达,抑制和延缓腰椎间盘退变的形成和发展。

Objective To get experimental lumbar degenerative intervertebral disc model and evaluate the expression of HIF-1α and the affect of dimethyl fumarate （ DMF） on the expression and function of HIF-1α . Methods The L4/L5 segment nucleus pulposus tissue was taken for detection of protein polysaccharides and the immunohistochemistry with HIF-1α after MRI scan of the rat model of lumbar degeneration. Results The results of MRI showed that there was a significant degeneration of the intervertebral disc nucleus in the group B, and the T2 weighted phase signal was decreased （P 〈 0. 05 ） . The immunohistochemistry showed that HIF-1α was strongly pos-itive in the nucleus of group C,the differences were statistically significant （P 〈0. 05） compared with two control groups. The proteo-glycan content in the nucleus pulposus was of all groups shown that proteoglycan contents in group A, B, C was （3. 28 ± 0. 03）, （2. 06 ± 0. 04 ）,（ 2. 06 ± 0. 05 ） ng·g-1 respectively. The difference between them was statistically significant （ P 〈0. 01 ）. Conclusions The high expression of HIF-1α in lumbar degenerative disc indicated that the expression of HIF-1α is closely related to the lumbar disc degenerative. Treatment with Dimethyl Fumarate inhibits the expression of HIF-1α and the development of experimental rat lumbar degenerative disc in vivo.