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目的:观察抗核抗体(ANA)和抗ds-DNA抗体对人脐静脉血管内皮细胞(HUVEC)细胞间黏附分子-1(ICAM-1)、单核细胞趋化因子-1(MCP-1)表达的影响及他汀类药物氟伐他汀(fluvastatin,flu)干预后的变化,以探讨ANA和抗ds-DNA抗体在系统性红斑狼疮(SLE)血管炎中的致病机制和flu对血管内皮保护作用。方法:体外培养HUVEC,收集女性SLE患者血清(以抗核抗体全套为依据,分3组:ANA阴性、ANA滴度1:80、ANA滴度1:80和抗ds-DNA抗体均阳性的患者每组各5例)及女性健康对照者血清作为干预因素,分为空白对照组、正常对照组、SLE血清组1、2、3和SLE血清与氟伐他汀共同干预组。应用免疫细胞化学和双抗体夹心ELISA法检测不同干预因素对HUVECICAM-1和MCP-1的蛋白表达影响。结果:正常对照组和SLE血清组1与空白对照组相比,ICAM-1和MCP-1蛋白表达差异无统计学意义(P>0.05);SLE血清组2和SLE血清组3的ICAM-1与MCP-1表达高于正常对照组和SLE血清组1(P均<0.01)。氟伐他汀(1×10-5mol/L)能显著降低SLE血清组2和SLE血清组3刺激的HUVEC表达ICAM-1与MCP-1(P<0.01,P<0.05)。结论:ANA阳性(滴度为1:80),尤其是ANA和抗ds-DNA抗体均阳性的SLE血清可激活HUVEC,使其细胞内和细胞培养上清液中ICAM-1和MCP-1的蛋白表达增加;ANA阴性的SLE血清不能激活HUVEC,不能使其细胞内和细胞培养上清液中ICAM-1和MCP-1的蛋白表达增加。氟伐他汀可下调激活的HUVEC表达ICAM-1和MCP-1。
OBJECTIVE: To observe the effect of anti-nuclear antibody (ANA) and anti-dsDNA antibody on the expression of ICAM-1, MCP-1 in human umbilical vein endothelial cells (HUVECs) And the changes of the statin fluvastatin (flu) after intervention to explore the pathogenesis of ANA and anti-ds-DNA antibodies in systemic lupus erythematosus (SLE) vasculitis and the effect of flu on vascular endothelial protection effect. Methods: HUVECs were cultured in vitro. Serum from female patients with SLE were collected (based on the complete set of antinuclear antibodies), patients were divided into three groups: ANA negative, ANA titer 1:80, ANA titer 1:80 and anti-ds DNA antibody positive 5 in each group) and female healthy controls were divided into blank control group, normal control group, SLE serum group 1, 2, 3 and SLE serum and fluvastatin combined intervention group. The effects of different interventions on the protein expression of HUVECICAM-1 and MCP-1 were detected by immunocytochemistry and double antibody sandwich ELISA. Results: There was no significant difference in the expression of ICAM-1 and MCP-1 between the normal control group and the SLE serum group 1 compared with the blank control group (P> 0.05); ICAM-1 of SLE serum group 2 and SLE serum group 3 Compared with normal control group and SLE serum group, the expression of MCP-1 was higher (P <0.01). Fluvastatin (1 × 10-5 mol / L) significantly reduced the expression of ICAM-1 and MCP-1 in HUVECs stimulated by SLE serum group 2 and SLE serum group 3 (P <0.01, P <0.05). CONCLUSIONS: ANA positive (titers of 1:80), especially SLE serum positive for both ANA and anti-dsDNA antibodies, activate HUVECs to produce ICAM-1 and MCP-1 in both intracellular and cell culture supernatants ANA-negative SLE serum could not activate HUVEC, and could not increase the protein expression of ICAM-1 and MCP-1 in its intracellular and cell culture supernatant. Fluvastatin can down-regulate the expression of ICAM-1 and MCP-1 in activated HUVECs.