护心通络方通过干预CETP介导脂质代谢抗兔动脉粥样硬化的实验研究

目的 探究护心通络方通过调控胆固醇脂转运蛋白（CETP）抗兔动脉粥样硬化（AS）的效果及作用机制。方法 将40只雄性新西兰兔按照随机数字表法分为空白对照组、AS模型组、辛伐他汀组0.33 mg/（kg·d）]、护心通络方组0.34 g/（kg·d）],每组10只。空白对照组予普通饲料喂养22周,其他3组予高脂饲料喂养14周后分组给药干预8周。实验前、给药14周、给药22周检测血清高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、三酰甘油（TG）水平。第22周末处死动物,分离胸主动脉,苏木素-伊红（HE）染色观察病理改变。实时荧光定量PCR法（qPCR）和蛋白免疫印迹检测肝脏腺苷三磷酸结合盒转运子1（ABCA1）、载脂蛋白A-I（apoA-I）和卵磷脂胆固醇脂酰转移酶（LCAT）表达水平。结果 实验前各组血清TC、TG、HDL-C、LDL-C水平差异均无统计学意义（P>0.05）。实验14周时,与空白对照组比较,AS模型组、辛伐他汀组、护心通络方组血清TC、TG、LDL-C水平升高,HDL-C水平下降（P<0.05）。实验22周时,与AS模型组相比,辛伐他汀组、护心通络方组血清TC、TG、LDL-C水平下降,HDL-C水平升高（P<0.05）。与空白对照组相比,AS模型组血清CETP表达水平升高;与AS模型组相比,辛伐他汀组和护心通络方组CETP水平降低。与空白对照组相比,AS模型组肝脏ABCA1、apoA-I、LCAT mRNA和蛋白表达水平降低。与AS模型组相比,辛伐他汀组和护心通络方组肝脏ABCA1、apoA-I和LCAT mRNA和蛋白水平升高（P<0.05）。结论 护心通络方可通过降低CETP水平,激活ABCA1/apoA-I/LCAT通路,最终提高HDL-C水平,改善兔动脉粥样硬化。

Experimental study of huxintongluo decoction on rabbit atherosclerosis by intervening CETP mediated lipid metabolism

Objective To study the effect and mechanism of huxintongluo decoction on rabbit atherosclerosis (AS) by regulating cholesterol lipid transporter protein (CETP). Methods Forty male New Zealand rabbits were divided into the blank control group, the AS model group, the simvastatin group 0.33 mg/(kg·d)] and the huxintongluo group 0.34 g/(kg·d)] according to random number table method, with 10 rabbits in each group. The blank control group was fed ordinary diet for 22 weeks. The other three groups were fed with high fat diet for 14 weeks, and then different drug intervention was performed in groups for 8 weeks. Serum levels of high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), total cholesterol (TC) and triglyceride (TG) were detected before the experiment, 14 and 22 weeks after administration. The animals were sacrificed at the end of the 22-week, the thoracic aorta was separated, and the pathological changes were observed by hematoxyl-eosin (HE) staining. The expression levels of ABCA1, apoA-I and LCAT in liver tissues were detected by fluorescence quantitative PCR and Western blot assay. Results There were no significant differences in serum levels of TC, TG, HDL-C and LDL-C before the experiment between the four groups (P>0.05). At week 14 of experiment, compared with the blank control group, serum levels of TC, TG and HDL-C were significantly increased in the other three groups, while the serum level of LDL-C was significantly decreased (P<0.05). At week 22 of experiment, compared with the AS model group, serum levels of TC, TG and LDL-C were significantly decreased in the other three groups, while serum level of HDL-C was significantly increased (P<0.05). Compared with the blank control group, the serum level of CETP increased in the AS model group. Compared with the AS model group, the serum level of CETP decreased in the simvastatin group and the huxintongluo group. Compared with the blank control group, ABCA1, apoA-I and LCAT mRNA and protein levels in liver tissues were decreased in the AS model group. Compared with the AS model group, mRNA and protein levels of ABCA1, apoA-I and LCAT were increased in the simvastatin group and the Huxintongluo group (P<0.05). Conclusion Huxintongluo decoction can activate ABCA1/apoA-I/LCAT pathway by reducing CETP level, ultimately improve HDL-C level and improve atherosclerosis in rabbits.