不同剂量氯沙坦对氧化修饰型低密度脂蛋白诱导的人单核巨噬细胞肝X受体及小凹蛋白mRNA表达的影响

Effects and mechanism of different doses of losartan on expressions of liver X receptor and caveolin-1 in cultured human monocyte-macrophage cells induced by oxidized low density lipoprotein

目的探讨不同剂量氯沙坦对氧化修饰型低密度脂蛋白（ox-LDL）诱导的人单核巨噬细胞肝X受体及小凹蛋白-1 mRNA表达的影响。方法采用体外密度梯度离心法分离健康人血单核细胞并培养至3-4代,以佛波酯诱导转化为巨噬细胞,用ox-LDL干预细胞使其转化为泡沫细胞,分别用不同剂量氯沙坦（10、50、75和100μmol/L）干预泡沫细胞,实时PCR检测各组肝X受体、小凹蛋白-1 mRNA的表达情况。结果与空白对照组比较,ox-LDL组肝X受体mRNA表达（0.26±0.02比1.00±0.02）、小凹蛋白-1 mRNA表达（0.27±0.01比1.00±0.04）均下调,差异有统计学意义（均为P〈0.05）;与ox-LDL组比较,随着氯沙坦剂量的升高,各氯沙坦组的肝X受体、小凹蛋白-1 mRNA表达逐渐上调,且呈剂量依赖性,差异均有统计学意义（均为P〈0.05）;不同剂量氯沙坦组之间进行两两比较,肝X受体、小凹蛋白-1 mRNA的表达差异均有统计学意义（均为P〈0.05）。结论氯沙坦可以逆转ox-LDL对人单核巨噬细胞肝X受体及小凹蛋白-1 mRNA表达的抑制,且呈一定的剂量依赖趋势。

Objective To investigate the influence of different doses of losartan on the expression of liver X receptor（ LXR） and caveolin-1 in cultured human monocyte-macrophage cells which were induced by oxidized low density lipoprotein（ ox-LDL）. Methods The mononuclear cells of healthy people were separated by using in vitro density centrifugation method and cultured to the 4th generation. Macrophages were induced by phorbol ester（ 160 nmol /ml） after 24 h culture. The human monocyte-macrophage cells were divided into six groups： control group,ox-LDL group,different doses of losartan group（ 10,50,75 and 100 μmol /L）. The expressions of LXR mRNA and caveolin-1 mRNA were detected by RT-PCR.Results Effects of different doses of losartan on expressions of LXR mRNA and caveolin-1 mRNA in cultured human monocyte-macrophage cells induced by ox-LDL： comparison among six groups,the differences were statistically significant（ F = 193. 813,159. 163,both P〈0. 001）. Compared with control group,the expressions of LXR mRNA（ 0. 26 ± 0. 02 vs. 1. 00 ± 0. 02） and caveolin-1 mRNA（ 0. 27 ± 0. 01 vs. 1. 00 ±0. 04） were significantly decreased in the ox-LDL group,and they were in a concentration-dependent manner（ all P〈0.05）. Compared with ox-LDL group,the expressions of LXR mRNA and caveolin-1 mRNA were significantly increased in different doses of losartan groups in dose-dependent manner（ all P〈0. 05）.Different doses of losartan were compared between groups（ between each group P〈0. 05）,the difference between each two groups was statistically significant（ P〈0. 05）. Conclusions Losartan can reverse the inhibition of the expressions of LXR and caveolin-1 mRNA in cultured human monocyte-macrophage cells induced by ox-LDL in a dose dependent manner.