基于代谢组学的“附子”提取物心脏毒性及机制研究。

Study on Cardiotoxicity and Mechanism of "Fuzi" Extracts Based on Metabonomics.

机构信息

Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China.

Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.

出版信息

Int J Mol Sci. 2018 Nov 7;19(11):3506. doi: 10.3390/ijms19113506.

To investigate the toxicity of water and ethanol "Fuzi" (FZ) extracts and to explore the toxicity mechanism in rats. Water and ethanol extracts were prepared. Three groups of rats received the water extract, ethanol extract, or water by oral gavage for seven days. Pathological section staining of heart tissue. Colorimetric analysis was used to determine serum lactate dehydrogenase. The metabolic expression of small molecules in rats was measured by a metabolomics method. Western blotting was used to detect the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), transforming growth factor-β1 (TGF-β1), and caspase-3. Immunohistochemistry was used to detect the expression of CTnI, mTOR, and TGF-β1. The water and ethanol FZ extracts exert cardiotoxic effects via activating the PI3K/Akt/mTOR signaling pathway to induce cardiomyocyte apoptosis.

目的

研究水提和醇提“附子”（Fuzi）提取物的毒性，并探讨其在大鼠体内的毒性机制。方法：制备水提物和醇提物。三组大鼠分别经灌胃给予水提物、醇提物或水，连续 7 天。心脏组织病理切片染色。采用比色法检测血清乳酸脱氢酶（lactate dehydrogenase，LDH）水平。采用代谢组学方法检测大鼠小分子的代谢表达。Western blot 检测磷酸肌醇 3-激酶（phosphoinositide 3-kinase，PI3K）、蛋白激酶 B（protein kinase B，Akt）、雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）、转化生长因子-β1（transforming growth factor-β1，TGF-β1）和半胱氨酸天冬氨酸蛋白酶 3（caspase-3）的表达。免疫组织化学法检测心肌肌钙蛋白 I（cardiac troponin I，cTnI）、mTOR 和 TGF-β1 的表达。结果：水提和醇提附子提取物通过激活 PI3K/Akt/mTOR 信号通路诱导心肌细胞凋亡，发挥心脏毒性作用。