| 杜 琎,石开虎,赵 扬,胡定辉,李 航,刘尊涛.丹参酚酸B通过抑制PI3K/AKT/mTOR通路促进自噬减轻大鼠心肌纤维化的研究[J].,2019,19(20):3812-3817 |
| 丹参酚酸B通过抑制PI3K/AKT/mTOR通路促进自噬减轻大鼠心肌纤维化的研究 |
| A Study of Reducing Rat Myocardial Fibrosis by Promoting the Autophagy Resulting from the Inhibition of PI3K/AKT/mTOR Pathway by Salvianolic acid B (SA-B) |
| 投稿时间：2019-03-13 修订日期：2019-04-09 |
| DOI：10.13241/j.cnki.pmb.2019.20.003 |
| 中文关键词: 丹参酚酸B 自噬 心肌纤维化 PI3K/AKT/mTOR Beclin1 LC3-II Western blot |
| 英文关键词: Salvianolic acid B Autophagy Myocardial fibrosis PI3K/AKT/ mTOR Beclin1 LC3-II Western blot |
| 基金项目:国家自然科学基金面上项目（81570295） |
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| 中文摘要: |
| 摘要 目的：研究丹参酚酸B（SA-B）能否通过抑制PI3K/AKT/mTOR通路促进自噬，从而减轻大鼠心肌纤维化。方法：选用SD大鼠40只，完全随机化分为对照组、模型组、低剂量SA-B治疗组和高剂量SA-B治疗组，采用皮下注射异丙肾上腺素（ISO）构建大鼠心肌纤维化模型。低、高剂量SA-B治疗组在造模同时灌喂丹参酚酸B水溶液，对照组和模型组分别灌胃等体积0.9%生理盐水。测定心重指数（HW/BW）和左心室重指数（LVW/BW）；ELISA法测定心肌中I型、III型胶原水平；Western blot检测自噬相关蛋白PI3K、AKT、p-AKT、mTOR、Beclin1、LC3-II水平；大鼠心肌HE染色评估心肌纤维化程度。结果：与对照组比较，模型组中大鼠的心重指数、左心室重指数和心肌中I型、III型胶原的水平升高（P<0.05），HE染色结果提示心肌组织发生明显的纤维化。模型组大鼠心肌细胞中的自噬相关蛋白PI3K、AKT、p-AKT 、mTOR表达升高，Beclin1、LC3-II表达较对照组明显降低（P<0.05）。SA-B组中心重指数、左心室重指数和心肌中I型、III型胶原的水平明显降低，HE染色未见明显纤维化病灶，其自噬相关蛋白PI3K、AKT、p-AKT 、mTOR表达降低，Beclin1、LC3-II表达较模型组明显升高（P<0.05）。结论：丹参酚酸B能够抑制ISO所致的大鼠心肌纤维化，且具有剂量依耐性，其机制与抑制PI3K/AKT/mTOR传导通路促进细胞自噬密切相关。 |
| 英文摘要: |
| ABSTRACT Objective: To investigative whether the salvianolic acid B (SA-B) could inhibit the PI3K/AKT/mTOR pathway to promote the autophagy, thereby reducing rat myocardial fibrosis. Methods: A total of 40 SD rats underwent the complete randomization and were assigned to four groups: the control group, model group, low-dose and high-dose SA-B group. The rat myocardial fibrosis model was established by subcutaneous injection of isoproterenol (ISO). For treatment groups with low- and high-dose SA-B, the modeling was performed while feeding rats with SA-B aqueous solution was conducted, and 0.9% of normal saline with the same volume was administrated in the control and model groups. The heart weight and body weight index (HW/BW) and left ventricular weight and body weight index (LVW/BW) were measured; the ELISA method was used to detect the type I and III collagen levels in myocardia; the levels of autophagy-related proteins, PI3K, AKT, p-AKT, mTOR, Beclin1, LC3-II were detected by using Western blot; the HE staining in rat myocardia was used for the assessment on the degree of myocardial fibrosis. Results: As compared with the control group, it showed an increase for the model group in HW/BW, LVW/BW and type I and III collagen levels in myocardia (P<0.05), and the results of HE staining suggested the significant fibrosis for myocardia. In the model group, it had an increase in expression levels of autophagy-related proteins, PI3K, AKT, p-AKT, mTOR and a significant decrease in expression levels of Beclin1 and LC3-II as compared with the control group (P<0.05). In the SA-B group, it showed an obvious decrease in HW/BW, LVW/BW and type I and III collagen levels in myocardia, and the HE staining suggested no significant fibrosis, and it showed a decrease for expression levels of autophagy-related proteins, PI3K, AKT, p-AKT, mTOR and significant increase for expression levels of Beclin1 and LC3-II as compared with the model group (P<0.05). Conclusion: The SA-B could inhibit rat myocardial fibrosis caused by ISO in a dose-dependent manner, and its mechanism was closely associated with autophagy promoting by the inhibition of PI3K/AKT/mTOR pathway. |
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