天麻醇提物调节小鼠肝脏胆固醇代谢的作用机制研究

Study on the mechanism of Gastrodia elata alcohol extract regulating cholesterol metabolism in mice liver

目的:从胆固醇吸收、肝脏胆固醇代谢途径探讨天麻醇提物降低血清胆固醇水平的作用机制。方法:蛋黄乳腹腔注射复制小鼠急性高脂血症模型,检测小鼠血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)的含量变化;脂肪乳灌胃建立小鼠肝脏脂质沉积模型,检测小鼠体质量变化、脏器指数、肝脂4项的变化,以HE染色及油红O染色观察肝组织病理变化;采用Western blot检测胆固醇生物合成相关蛋白LXRα和SREBP1、细胞摄取相关蛋白LDLR、外排流出相关蛋白ABCG1及分解排泄相关蛋白CYP7A1,探讨天麻醇提物调节肝脏胆固醇代谢的机制。结果:对比模型组,天麻醇提物组急性高脂血症模型小鼠的血清TC、TG含量无明显变化(P>0.05);肝脏脂质沉积模型小鼠肝脏指数(P<0.05)及肝组织TC、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)含量明显降低(P<0.01),HE染色与油红O染色结果显示肝组织病变、脂质沉积程度明显减轻;天麻醇提物能降低模型小鼠肝组织LXRα、SREBP1表达量(P<0.01),上调LDLR、CYP7A1的表达(P<0.05),对ABCG1表达量无明显影响。结论:天麻醇提物通过降低肝脏TC的生物合成和增强肝脏TC细胞摄取和分解排泄而降低血清TC水平。

OBJECTIVE To investigate the mechanism of Gastrodia elata alcohol extract decreasing serum cholesterol level from cholesterol absorption and liver cholesterol metabolism.METHODS The acute hyperlipidemia model of mice was established by intraperitoneal injection of yolk milk,and the changes of serum total cholesterol and triglyceride were detected.The liver lipid deposition model of mice was established by intragastric administration of fat emulsion.The changes of body weight,organ index and liver lipid were detected.The pathological changes of liver tissue were observed by HE staining and oil red O staining.Western blot was used to detect cholesterol biosynthesis related proteins LXRαand SREBP-1,cellular uptake related protein LDLR,efflux related protein ABCG1 and decomposition excretion related protein CYP7 A1,and to explore the mechanism of Gastrodia elata alcohol extract regulating liver cholesterol metabolism.RESULTS Compared with the model group,there were no significant changes in serum TC and TG contents in the acute hyperlipidemia model mice in Gastrodia elata alcohol extract group(P>0.05).The liver index(P<0.05),TC and LDL-C contents(P<0.01)in liver tissue of liver lipid deposition model mice were significantly decreased.The HE staining results showed that the pathological changes of liver tissue were significantly reduced,and the oil red O staining results showed that the lipid deposition of liver tissue was significantly reduced.Gastrodia elata alcohol extract could reduce the expression levels of LXRαand SREBP1(P<0.01)in liver tissue of model mice,up-regulate the expression levels of LDLR and CYP7 A1(P<0.05),and had no significant effect on the expression level of ABCG1.CONCLUSION Gastrodia elata alcohol extract reduces serum TC level by reducing liver TC biosynthesis and enhancing liver TC cell uptake and decomposition excretion.