Phillyrin Inhibits Isoproterenol-Induced Cardiac Hypertrophy Via P38 and NF-κB Pathways
Phillyrin Inhibits Isoproterenol-Induced Cardiac Hypertrophy Via P38 and NF-κB Pathways
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DOI：
10.1177/1934578x221144581
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发表时间：
2022-12
影响因子：
1.8
通讯作者：
Juanjuan Liu;Jiahang Li;Shengqian Yang;Yuanting She;Xiaohui Li;Yi-Yang Jia
中科院分区：
文献类型：
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作者：
Juanjuan Liu;Jiahang Li;Shengqian Yang;Yuanting She;Xiaohui Li;Yi-Yang Jia
心肌肥厚是对慢性心脏应激的主要代偿反应，常进展到失代偿状态，有可能导致心力衰竭。连翘苷(Phillyrin，PHI)是从连翘中提取的一种新型化合物，对糖尿病肾病具有抗炎、抗病毒和肾脏保护作用。因此，我们研究了PHI对异丙肾上腺素(ISO)诱导的CH的影响。用异丙肾上腺素诱导体内心肌肥大，并用异丙肾上腺素处理H9C2细胞。异丙肾上腺素治疗7天和14天可减轻异丙肾上腺素所致小鼠的脑出血。超声心动图显示PHI改善了异丙肾上腺素诱导的CH心功能和结构。Phi显著降低了ISO治疗小鼠的心脏重量/体重(HW/BW)和心脏重量/胫骨长度(HW/TL)比率，并改善了左心(LV)功能。苏木精-伊红染色显示ISO组心肌细胞面积在第7天和第14天显著增加，PHI显著降低，PHI-100组明显优于PHI-50组。天狼星红染色显示PHI可显著减少ISO诱导的心肌横切面胶原沉积，并抑制ISO诱导的小鼠血清cTn-I和NT-proBNP的表达。H9C2细胞的体外实验数据显示，苯丙氨酸可显著降低异丙肾上腺素诱导的细胞面积和细胞总蛋白水平，同时显著抑制心钠素、脑钠素、IL-6和IL-1β的表达。此外，在体内和体外，PHI同时抑制P65和P38的磷酸化。综上所述，本研究证实了苯丙氨酸在体内和体外对脑出血的保护作用，该作用与激活P38/NF-κB途径抑制炎症有关。
Cardiac hypertrophy (CH) is the main compensatory response to chronic heart stress and often progresses to a decompensation state potentially leading to heart failure. Phillyrin (PHI) is a novel compound derived from Forsythia, which has shown anti-inflammatory and anti-virus activities as well as renal protective effects on diabetic nephropathy. Therefore, we investigated the effects of PHI on CH induced by isoproterenol (ISO). Cardiac hypertrophy was induced by ISO in vivo, and the H9C2 cells were treated with ISO. PHI treatment alleviated CH in isoproterenol-induced mice in 7 and 14 days. Echocardiography showed that the PHI improved ISO-induced CH heart function and structure. PHI significantly decreased heart weight/body weight (HW/BW) and heart weight/tibia length (HW/TL) ratios and improved left ventricular (LV) function in ISO-treated mice. Hematoxylin and eosin staining revealed cardiomyocyte areas of the ISO group were significantly increased, and PHI was significantly reduced at 7 and 14 days, PHI-100 groups showed significantly better improvements than PHI-50. Sirius red staining indicated PHI significantly decreased collagen deposition in heart cross-sections induced by ISO, and PHI repressed ISO-induced cTn-I and NT-proBNP expression in mouse serum. In vitro data from H9C2 cells showed that PHI decreased cell areas and total cell protein levels in cells induced by ISO, whereas ANP, BNP, IL-6, and IL-1β expression was significantly inhibited by PHI. Also, PHI simultaneously inhibited P65 and P38 phosphorylation in vivo and in vitro. In conclusion, this study demonstrated the protective effect of PHI on CH in in vivo and in vitro, and this effect was related to the suppression of inflammation through the activation of the P38/NF-κB pathway.