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目的:观察非诺贝特对高胆固醇血症兔脂肪组织组织因子(TF)mRNA表达的影响,并阐明其可能机制。方法:15只新西兰大白兔随机分为3组,对照组、高胆固醇血症组和非诺贝特治疗组。实验的第12周末取兔皮下脂肪组织,并分离培养脂肪细胞,应用半定量逆转录多聚酶链式反应(RT-PCR)测定脂肪组织和细胞TF、PPARγ和PPARαmRNA的表达。结果:RT-PCR结果显示高胆固醇血症组脂肪组织TFmRNA表达高于对照组(1.149±0.014vs1.034±0.011,P<0.01)。非诺贝特干预4周后,该组脂肪组织TFmRNA表达明显低于高胆固醇血症组(1.017±0.010vs1.149±0.014,P<0.01)。与对照组比较,高胆固醇血症组脂肪组织PPARγmRNA表达显著升高(0.575±0.141vs0.425±0.082,P<0.05),非诺贝特能降低高胆固醇饲养兔脂肪组织PPARγmRNA表达(0.478±0.110vs0.575±0.141,P<0.05)。3组兔脂肪组织PPARαmRNA表达差异无统计学意义。在培养的脂肪细胞,非诺贝特呈浓度依赖性地降低脂肪细胞TF和PPARγmRNA表达。结论:非诺贝特能抑制高胆固醇饲养兔脂肪组织TFmRNA表达,其机制之一可能与下调脂肪细胞PPARγmRNA表达有关。
Objective: To observe the effect of fenofibrate on the expression of tissue factor (TF) mRNA in adipose tissue of hypercholesterolemic rabbits and to elucidate its possible mechanism. Methods: Fifteen New Zealand white rabbits were randomly divided into three groups: control group, hypercholesterolemia group and fenofibrate treatment group. Rabbit subcutaneous adipose tissue was harvested at the end of the 12th week, and adipocytes were isolated and cultured. The expression of TF, PPARγ and PPARαmRNA in adipose tissue and cells were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results: RT-PCR results showed that TF mRNA expression in adipose tissue of hypercholesterolemia group was higher than that of control group (1.149 ± 0.014vs1.034 ± 0.011, P <0.01). After 4 weeks of fenofibrate intervention, TFmRNA expression in adipose tissue of this group was significantly lower than that of hypercholesterolemia group (1.017 ± 0.010vs.1.149 ± 0.014, P <0.01). Compared with the control group, PPARγmRNA expression was significantly increased in hypercholesterolemia adipose tissue (0.575 ± 0.141 vs0.425 ± 0.082, P <0.05), and fenofibrate could reduce PPARγmRNA expression in adipose tissue of hypercholesterolemic rabbits (0.478 ± 0.110 vs0.575 ± 0.141, P <0.05). There was no significant difference in the expression of PPARαmRNA among three groups of rabbit adipose tissue. In cultured adipocytes, fenofibrate decreased adipocyte TF and PPARγ mRNA expression in a concentration-dependent manner. Conclusion: Fenofibrate can inhibit TFmRNA expression in adipose tissue of rabbits fed with high cholesterol, and one of the mechanisms may be related to downregulation of PPARγmRNA in adipocytes.