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目的:探讨高同型半胱氨酸血症(HHcy)对大鼠主动脉平滑肌细胞中巨噬细胞炎性蛋白1α(MIP-1α)和CC型趋化因子受体1(CCR1)表达的影响及机制。方法:将16只SD大鼠随机分为正常对照组和HHcy组。正常对照组给予普通饲料喂养,HHcy组在普通饲料基础上加2蛋氨酸喂养。60d后,采用高压液相色谱法测定血浆同型半胱氨酸(Hcy)浓度,采用免疫组织化学方法检测主动脉平滑肌细胞中MIP-1α、CCR1、核转录因子-κB(NF-κB)蛋白的表达,采用RT-PCR法检测主动脉平滑肌细胞中MIP-1α、CCR1mRNA的表达。结果:HHcy组血浆Hcy浓度(45.74±9.65)mmol/L明显高于正常对照组(7.38±2.28)mmol/L,P<0.01;HHcy组主动脉平滑肌细胞中的MIP-1α、CCR1蛋白及mRNA表达均较正常对照组明显增加(P<0.01);HHcy组主动脉平滑肌细胞中NF-κBP65蛋白的表达显著高于正常对照组(P<0.01)。结论:HHcy可能通过激活NF-κB诱导SD大鼠主动脉平滑肌细胞表达MIP-1α及受体CCR1增多,进而诱发动脉粥样硬化形成。
Objective: To investigate the effects of hyperhomocysteinemia (HHcy) on the expression of macrophage inflammatory protein-1α (MIP-1α) and chemokine receptor type 1 (CCR1) in rat aortic smooth muscle cells mechanism. Methods: Sixteen SD rats were randomly divided into normal control group and HHcy group. The normal control group was fed with normal feed, and HHcy group was fed with 2 methionine on the basis of normal feed. After 60 days, the plasma homocysteine (Hcy) concentration was measured by high pressure liquid chromatography. The expression of MIP-1α, CCR1, NF-κB protein in aortic smooth muscle cells was detected by immunohistochemistry The expression of MIP-1α and CCR1 mRNA in aortic smooth muscle cells was detected by RT-PCR. Results: The Hcy concentration (45.74 ± 9.65) mmol / L in HHcy group was significantly higher than that in normal control group (7.38 ± 2.28 mmol / L, P <0.01). The levels of MIP-1α and CCR1 protein and mRNA in aortic smooth muscle cells (P <0.01). The expression of NF-κBp65 in aortic smooth muscle cells of HHcy group was significantly higher than that of the normal control group (P <0.01). Conclusion: HHcy may induce the formation of atherosclerosis by activating the NF-κB-induced increase of MIP-1α and CCR1 in aortic smooth muscle cells of SD rats.