PPARα、PPARγ的上调参与淫羊藿苷对自发性高血压大鼠心室重构的调节

Icariin attenuates left ventricular remodeling in SHR by up-regulating PPARα and PPARγ

目的观察淫羊藿苷(icariin,Ica)对自发性高血压大鼠(SHR)心室重构的作用,并探讨其机制。方法 14周龄♂SHR大鼠21只随机分为模型组,Ica低、高剂量组(20、40mg·kg-1,ig,bid),14周龄♂WKY大鼠为空白对照组,空白对照组和模型组给予等体积的双蒸水灌胃。适应性喂养1周,连续灌胃12周后处死全部动物,采用双抗体夹心法测定左心羟脯氨酸的含量;Masson染色观察左心室组织病理学变化;real-time RT-PCR、Western blot分别检测PPARα、PPARγm RNA和蛋白的表达。结果与空白对照组相比,模型组出现心室重构,心肌纤维化,心肌组织羟脯氨酸含量明显上升(P<0.01),PPARα、PPARγm RNA和蛋白表达明显降低(P<0.05或P<0.01)。与模型组相比,Ica低、高剂量组心肌细胞排列较整齐,心肌纤维化减少,且心肌羟脯氨酸含量降低,PPARα、PPARγm RNA和蛋白表达升高(P<0.05或P<0.01)。结论淫羊藿苷具有减轻自发性高血压大鼠心室重构的作用,其机制可能与上调PPARα、PPARγ有关。

Aim To investigate the effect of Icariin （Ica） on remodeling of left ventricular in SHR and ex- plore the mechanism. Methods Twenty-one male SHR aged 14 weekswere randomly divided into model group （ n = 7 ）, low-dose of Ica-treated group （ 20 mg · kg-1. bid, n = 7 ）, high-dose of Ica-treated group （40 mg · kg-1. bid, n = 7） , and WKY as control group （ n = 7 ）. Low- and high-dose of Ica-treated groups were given Ica from the age of 14 weeks to 26 weeks. The other rats in the model group and control group were given the same amount of double distilled water. Then, the content of hydroxyproline （Hyp） was measured by ELISA. The morphological changes of the left ventricu- lar were observed by Masson staining. The mRNA and the protein expression of PPARα and PPAR γwere ex- amined by real time RT-PCR and Western blot tech- nique respectively. Results Compared with the nor-real control group, interstitium fibrosis and myofibrilla were lined up in disorder; the content of Hyp was in- creased and the mRNA and protein expression of PPARα and PPARγ, were down-regulated in model group（P 〈 0. 01 ）. Compared with the model group, the myocardial ceils were arranged less disorderly and the myocardial fibrosis was reduced; the content of Hyp was decreased in low-and high-dose of Ica-treated groups（P 〈0. 01 orP 〈0. 05） ; the mRNA and protein expression of PPARα and PPARγ were up-regulated in low- and high-dose of Ica-treated groups （P 〈 0.01 or P 〈 0.05 ）. Conclusion Ica may attenuate left ven- tricular remodeling in SHR by up-regulating PPARα and PPARγ.