烟酸对实验性动脉粥样硬化兔协同刺激分子B7-H3和B7-H4表达的影响

Effects of niacin on the expression of synergistic stimulatory molecules B7-H3 and B7-H4 in experimental atherosclerotic rabbits

目的:探讨烟酸对实验性动脉粥样硬化(As)兔协同刺激分子B7-H3和B7-H4表达的影响。方法:选取30只成年雄性新西兰大白兔随机分为对照组、As组和烟酸组。As组持续高脂饮食14周,烟酸组在高脂饮食8周基础上给予烟酸200 mg/(kg·d)干预6周,对照组普通饮食14周。实验前、实验后0周、8周及14周采集静脉血,实验结束时留取主动脉。全自动生化分析仪检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,HE法检测主动脉斑块病理改变,酶联免疫吸附试验(ELISA)检测血清白细胞介素(IL)-1β、γ-干扰素(IFN-γ)、IL-10、可溶性B7-H3(sB7-H3)及可溶性B7-H4(sB7-H4)水平,实时荧光定量PCR检测外周血单核细胞和主动脉B7-H3、B7-H4 mRNA的表达。结果:As组血清TC、TG、LDL-C、IL-1β和IFN-γ水平及主动脉斑块面积均明显高于对照组,而血清IL-10、sB7-H3和sB7-H4水平及外周血单核细胞和主动脉B7-H3、B7-H4 mRNA的表达水平均显著低于对照组,差异均有统计学意义(P<0.05)。烟酸组血清TC、TG、LDL-C、IL-1β和IFN-γ水平及主动脉斑块面积均明显低于As组,而血清HDL-C、IL-10、sB7-H3和sB7-H4水平及外周血单核细胞和主动脉B7-H3、B7-H4 mRNA的表达水平均显著高于As组,差异均有统计学意义(P<0.05)。结论:烟酸可能通过促进B7-H3、B7-H4表达,调节炎性因子IL-1β、IFN-γ、IL-10水平,从而抑制As兔的炎性反应。

Objective To investigate the effect of niacin on the expression of B7-H3 and B7-H4 synergistic stimulatory molecules of atherosclerosis(As)in rabbits.Method Thirty adult male of New Zealand white rabbits were randomly divided into the control group,As group and niacin group.The As group continued to receive high-fat diet for 14 weeks,and the niacin group received 200 mg/(kg·d)of niacin for 6 weeks on the top of the high-fat diet for 8 weeks,the control group received regular diet for 14 weeks.Venous blood was collected at 0,8 and 14 weeks before and after the experiment,and the aorta was retained at the end of the experiment.The serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were measured by automatic biochemical analyzer.The pathological changes of aortic plaque were detected by HE.The serum levels of interleukin 1β(IL-1β),interferon gamma(IFN-γ),interleukin 10(IL-10),soluble B7-H3(sB7-H3)and soluble B7-H4(sB7-H4)were detected by ELISA.,and the mRNA expressions of B7-H3 and B7-H4 in peripheral blood monocytes and aorta were detected by RT-PCR.Results The serum levels of TC,TG,LDL-C,IL-1β,IFN-γand aortic plaque area of As group were significantly higher than the control group(P<0.05),while the serum levels of IL-10,sB7-H3,sB7-H4 and the mRNA levels of B7-H3 and B7-H4 in peripheral blood monocytes and aortic were significantly lower than the control group(P<0.05);The serum levels of TC,TG,LDL-C,IL-1β,IFN-γand aortic plaque area of the niacin group were significantly lower than As group(P<0.05),while the serum levels of HDL-C,IL-10,sB7-H3,sB7-H4 and the mRNA levels of B7-H3 and B7-H4 in peripheral blood monocytes and aorticlevels were significantly higher than As group(P<0.05).Conclusion Niacin may inhibit the inflammatory response in rabbits with As via promoting the expression of B7-H3,B7-H4 and regulating the levels of inflammatory factors IL-1β,IFN-γand IL-10.