替米沙坦对肝脏和骨骼肌细胞脂蛋白脂肪酶表达的影响

Effects of telmisartan on lipoprotein lipase expression in hepatic and muscular cells

目的通过观察替米沙坦对HepG2细胞和C2C12细胞过氧化物酶体激增剂激活受体(PPAR)α和脂蛋白脂肪酶(LPL)表达的影响,以探讨其改善脂肪酸代谢的机制。方法在HepG2细胞和诱导成熟后的C2C12细胞中加入不同浓度的替米沙坦培养48h以及同一浓度替米沙坦作用的不同时间,应用RT-PCR方法检测PPAR-α和LPLmRNA的表达,用Western blot杂交法检测PPARα和LPL蛋白的表达。然后在HepG2细胞血用PPARα选择性拮抗剂MK886阻断替米沙坦作用,24h后观察LPLmRNA的表达。结果 (1)替米沙坦呈剂量和时间依赖性增强HepG2细胞中PPARα和LPLmRNA和其蛋白质的表达,但对C2C12中PPARα和LPL的表达无明显影响。(2)替米沙坦对HepG2细胞中LPLmRNA的上调作用可以被MK886抑制。结论替米沙坦在人类肝脏细胞中可以同时上调PPARα和LPL的表达,并且对LPL的调节作用是通过PPARα介导的。

Objective To investigate the effects of telmisartan on lipoprotein lipase （LPL） expression in HepG2 cells and muscle cells. Methods HepG2 （hepatic）cells and differentiated C2C12 （muscle） cells were treated with various concentration of telmisartan for 48h and with different time of telmisartan action at the same concentration. The expression levels of PPARa and LPL mRNAs were determined by RT-PCR, and the the protein expression levels of PPARa and LPL were determined by Western blot. Then LPL mRNA expression of HepG2 was observed after co treatment with a selective PPARa antagonist （MK886） plus telmisarton for 24h. Results The mRNA and protein expressions of PPARa and LPL were increased by telmisartan in a concentration- and time dependent manners in HepG2 cell, but not in differentiated C2C12 cell. Upregulation of LPL mRNA expression by telmisartan was inhibited by MK886. Conclusions Telmisartan increases expression levels of PPARa and LPL in human liver, and the upregulation of LPL expression by telmisartan is PPARa-dependent.