叶酸对高同型半胱氨酸血症大鼠单核细胞趋化蛋白-1和白细胞介素-8释放的影响

Effects of folic acid on release of monocyte chemoattractant protein-1 and interleukin-8 in rats with hyperhomocysteinemia

目的:探讨叶酸(FA)对高同型半胱氨酸(Hhcy)血症大鼠释放单核细胞趋化蛋白1(MCP1)和白细胞介素8(IL8)的影响。方法:SD大鼠30只随机分3组:Hhcy组、FA组、正常对照组,每组10只,分别给予普通饲料加1.7%蛋氨酸、普通饲料加1.7%蛋氨酸和0.006%的FA、普通饲料,饲养45d,采用高效液相色谱法测定血浆总同型半胱氨酸(thcy)水平,双抗体夹心ELISA法测定大鼠血浆和oxLDL诱导的外周血单核细胞(PBMCs)释放MCP1和IL8的含量。结果:①大鼠喂高蛋氨酸饲料45d可诱导Hhcy,同时补充FA可显著降低血浆thcy水平(P<0.01);②与正常对照组相比,Hhcy组大鼠血浆thcy升高的同时,血浆和oxLDL诱导PBMCs释放的MCP1水平均明显升高(P<0.05;P<0.01),PBMCs释放的IL8水平亦明显升高(P<0.05),而血浆IL8的水平无明显变化(P>0.05);③FA组大鼠较Hhcy组大鼠血浆thcy水平降低,同时血浆和oxLDL诱导PBMCs释放MCP1的水平均显著降低(P<0.05;P<0.01),PBMCs释放的IL8水平亦明显降低(P<0.05),而血浆IL8的水平无明显变化(P>0.05)。结论:FA治疗显著降低血浆thcy和Hhcy血症大鼠体内MCP1和IL8的释放,FA可能通过下调趋化因子介导的炎症反应来阻止Hhcy诱导的早期动脉粥样硬化的发生。

Objective:To investigate effects of supplementation of folic acid on the release of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in the rats with hyperhomocysteinemia (Hhcy). Method:Thirty male SD rats were randomly divided into 3 groups (n=10 for each group): Hhcy group, folic acid treatment (FA) group and control group. They were fed respectively with normal diet enriched by 1.7% methionine (Met), normal diet plus 1.7% Met and 0.006% folate, normal diet for 45 days. The levels of total plasma homocysteine (thcy) were measured by high performance liquid chromatography. The concentrations of MCP-1 and IL-8 in plasma and release from peripheral blood mononuclear cells (PBMCs) stimulated by oxidized low density lipoprotein (ox-LDL) were detected by enzyme immunoassays. Result:①A high Met diet for!45 days was sufficient to induce Hhcy and folic acid supplementation prevented an elevation of thcy levels in the blood (P< 0.01). ② Levels of MCP-1 in plasma and in PBMCs stimulated by ox-LDL significantly elevated in Hhcy group (P< 0.05; P< 0.01). IL-8 released from PBMCs also increased in this group (P< 0.05) and the levels in plasma had no significant difference (P> 0.05).③During folate treatment, normalization of thcy levels was accompanied by a marked reduction of MCP-1 in plasma and in PBMCs stimulated by ox-LDL (P< 0.05; P< 0.01). IL-8 released from PBMCs also decreased (P< 0.05) and the levels in plasma had no significant difference (P> 0.05). Conclusion:Folic acid supplementation prevente an elevation of homocysteine levels in the blood. It also reduce the release of MCP-1 and IL-8 in the rats with Hhcy. Thus chemokines-mediated inflammatory process and formation of early atherosclerosis induce by Hhcy can be suppressed by folic acid.