化瘀祛痰方通过PI3K/Akt/mTOR信号通路调控自噬改善动脉粥样硬化家兔肝脏脂质损伤  

Effect of Huayu Qutan Decoction Recipe on Liver Lipid Injury in Atherosclerotic Rabbits by Regulating Autophagy Through PI3K/Akt/mTOR Signal Pathway

作　　者：满艺璁 杨灿 王雪婷[1] 王越尔 胡服 宋囡 陈丝 陈宁[1] 王健[1] 高云飞 贾连群[1,2] MAN Yicong;YANG Can;WANG Xueting;WANG Yueer;HU Fu;SONG Nan;CHEN Si;CHEN Ning;WANG Jian;GAO Yunfei;JIA Lianqun(Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications,Shenyang 110847,Liaoning,China;Major Scientific Research Platform of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)

机构地区：[1]中医脏象理论及应用教育部重点实验室,辽宁沈阳110847 [2]辽宁中医药大学重大科研平台,辽宁沈阳110847

出　　处：《中华中医药学刊》2019年第8期1913-1916,I0016,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81774022);辽宁省高等学校创新团队支持计划项目(LT2016012);辽宁省教育厅大学生创新创业训练计划项目(201710162000043)

摘　　要：目的:以PI3K/Akt/mTOR信号通路为切入点探讨化瘀祛痰方调控自噬改善动脉粥样硬化家兔肝脏脂质损伤的分子机制。方法:60只新西兰雄性大耳白家兔随机分为正常组、模型组、化瘀祛痰方组、辛伐他汀组,每组15只。正常组给予普通家兔饲料喂养,其他各组一次性静脉注射牛血清白蛋白(250 mg/kg)后以高脂饲料喂养以建立动脉粥样硬化模型,化瘀祛痰方组给予方药剂量为8 g·kg^-1·d^-1,辛伐他汀组给药量为1.4 mg·kg^-1·d^-1,正常组、模型组给予等体积生理盐水灌胃。4周后,HE染色观察各组家兔肝脏形态变化;全自动生化分析仪检测血清TC、TG、LDL-C、HDL-C含量变化;WB法检测肝脏PI3K、Akt、p-Akt、mTOR蛋白表达。结果:与正常组比较,模型组家兔肝脏脂肪变性明显,血清TC、TG、LDL-C水平显著升高(P<0.01),HDL-C水平显著降低(P<0.01),PI3K、Akt、mTOR蛋白表达水平下调(P<0.01);与模型组比较,化瘀祛痰方组和辛伐他汀组肝脏脂肪变性呈不同程度恢复,血清中TC、TG、LDL-C水平显著降低(P<0.01),HDL-C水平显著升高(P<0.01),PI3K、Akt、mTOR蛋白表达水平显著上调(P<0.05或P<0.01)。结论:化瘀祛痰方可通过PI3K/Akt/mTOR信号通路,调控动脉粥样硬化家兔肝脏自噬稳态,减缓肝脏脂质损伤,进而改善动脉粥样硬化。Objective: To explore molecular mechanism of the prevention and treatment to atherosclerosis by Huayu Qutan Decoctionby taking the PI3 K/Akt/mTOR signaling pathway autophagy as the breakthrough point. Methods:Sixty New Zealand male Large-eared white rabbits were randomly divided into normal group, model group, Huayu Qutan Decoction group and Simvastatin group, 15 in each group. The normal group was prepared by ordinary rabbit feeding every day and the other group was intravenously injected with bovine serum albumin(250 mg/kg) once and then fed with high-fat diet to establish atherosclerosis models. When finishing the model establishment, Huayu Qutan Decoction group was given 8 g·kg^-1·d^-1, the dosage of Simvastatin group was 1.4 mg·kg^-1·d^-1, and the normal group and the model group were given the same volume of saline orally.Four weeks later, the morphological changes of liver were observed by HE staining in each group. The changes of serum TC, TG, LDL-C and HDL-C in rabbits were detected by automatic biochemical analyzer. The expression levels of PI3 K, Akt, p-Akt and mTOR in liver of rabbits were detected by WB. Results: Compared with the normal group, the liver steatosis of the model group was obvious.The levels of TC, TG and LDL-C increased significantly(P<0.01) and the level of HDL-C decreasedsignificantly(P<0.01). The expression levels of PI3 K, p-Akt and mTOR were down-regulated(P<0.01).Compared with the model group, the liver steatosis of rabbits in the Huayu Qutan Decoction group and Simvastatin group recovered in different degrees. The levels of TC, TG and LDL-C decreased significantly(P<0.01) and the level of HDL-C increasedsignificantly(P<0.01). The expression level of PI3 K/Akt/mTOR pathway protein was up-regulated(P<0.05 or P<0.01).Conclusion: Huayu Qutan Decoction can regulate the level of hepatic autophagy homeostasisin ASrabbits through PI3 K/Akt/mTOR signaling pathway, slow down liver lipid damageand then improve atherosclerosis.

关 键 词：动脉粥样硬化 血脂异常 肝脏脂质损伤 自噬 

分 类 号：R285.5[医药卫生—中药学]