Icariside II improves myocardial fibrosis in spontaneously hypertensive rats by inhibiting collagen synthesis
Icariside II improves myocardial fibrosis in spontaneously hypertensive rats by inhibiting collagen synthesis
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艾卡瑞苷 II 通过抑制胶原蛋白合成改善自发性高血压大鼠的心肌纤维化
DOI：
10.1111/jphp.13190
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发表时间：
2019-12-09
影响因子：
3.3
通讯作者：
Yang, Danli
中科院分区：
文献类型：
--
作者：
Fu, Shu;Li, Yeli;Yang, Danli
目的观察淫羊藿苷II（ICS II）对自发性高血压大鼠（SHR）心肌纤维化的影响，并探讨其可能的机制。方法我们使用SHR作为动物模型，并且我们连续12周通过灌胃经口给予ICS II（4、8或16 mg/kg）（Fu等人，Biomed Pharmacother 2018; 100：64）。苏木精-伊红（HE）染色观察大鼠左心室形态。Masson三色染色检测心肌间质纤维化的发生。通过蛋白质印迹法检测α平滑肌肌动蛋白（α-SMA）、胶原蛋白I、III、基质金属蛋白酶2和9（分别为MMP-2和MMP-9）、金属蛋白酶组织抑制剂1（TIMP-1）、转化生长因子-β 1（TGF-β 1）、磷酸化Smad 2（p-Smad 2）、磷酸化Smad 3（p-Smad 3）和磷酸化p38（p-p38）的蛋白水平。结果表明，ICS II改善了心肌间质和血管周围胶原沉积，降低了胶原I/III和α-SMA表达。ICS II（8和16 mg/kg）下调MMP-2和MMP 9的表达，上调TIMP 1的表达。此外，ICS II处理降低了p-Smad 2/3、TGF-β 1和p-p38的蛋白水平。结论ICS Ⅱ可通过MMP/TIMP-1和TGF-β 1/Smad 2，3/p-p38信号通路抑制I型胶原和III型胶原的表达，对心肌纤维化有治疗作用。
Objectives We aimed to investigate the effects of icariside II (ICS II) on myocardial fibrosis in spontaneously hypertensive rats (SHRs) and to explore the possible mechanisms. Methods We used SHRs as animal models, and we administered ICS II (4, 8 or 16 mg/kg) orally by gavage for 12 consecutive weeks (Fu et al., Biomed Pharmacother 2018; 100: 64). The left ventricular morphology of the rats was observed using haematoxylin-eosin (HE) staining. The occurrence of myocardial interstitial fibrosis was detected by Masson's trichrome staining. The protein levels of alpha smooth muscle actin (alpha-SMA), Collagen I, III, matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively), tissue inhibitor of metalloproteinase 1 (TIMP-1), transforming growth factor-beta 1 (TGF-beta 1), phospho-Smad2 (p-Smad2), phospho-Smad3 (p-Smad3) and phospho-p38 (p-p38) were examined by Western blotting. Key findings The results suggested that ICS II improved myocardial interstitial and perivascular collagen deposition and decreased Collagen I/III and alpha-SMA expression. ICS II (8 and 16 mg/kg) downregulated the expression of MMP-2 and MMP9 and upregulated the expression of TIMP1. In addition, the protein levels of p-Smad2/3, TGF-beta 1 and p-p38 were decreased by ICS II treatment. Conclusions The results suggest that ICS II can inhibit the expression of Collagen I and Collagen III through the MMP/TIMP-1 and TGF-beta 1/Smad2,3/p-p38 signalling pathways and that it has therapeutic effects on myocardial fibrosis.