熊胆救心丸对高脂血症大鼠脂代谢紊乱的调节作用及机制

Effects and mechanisms of Xiongdan Jiuxin pills on regulating lipid dysmetabolism in hyperlipidemic rats

目的研究熊胆救心丸(XJP)对高脂血症大鼠血脂水平、肝功能、血管内皮及心脏的影响及潜在作用机制。方法采用高脂饲料喂养法建立高脂血症大鼠模型。将SD大鼠随机分为对照组、模型组、辛伐他汀组(4 mg·kg^(-1)SIM)和XJP剂量组(低、中高剂量分别为7.875、15.75、31.5 mg·kg^(-1))。每日灌胃给药,连续给药9周后,检测血清中胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、一氧化氮(NO)、内皮素-1(ET-1)、胆固醇酯转移蛋白(CETP)的含量和谷草转氨酶(AST)、谷丙转氨酶(ALT)、羟甲基戊二酸单酰辅酶A还原酶(HMGCR)的活性,以及肝脏TC、TG的含量与酰基转移酶(ACAT)的活性。HE染色法检查肝脏、主动脉及心脏的病理学改变。结果与模型组比较,药物治疗9周后,SIM组和XJP各剂量组大鼠血清中TC、TG、LDL-C、ET-1、CETP的含量及AST、ALT、HMGCR的活性和肝脏中TC、TG的含量及ACAT的活性均有不同程度降低,而血清中HDL-C、NO的含量升高。药物治疗组大鼠肝脏、主动脉及心脏的病理学改变均有不同程度减轻,其中,SIM组和XJP中剂量组的肝脏细胞结构较完整,大泡性脂滴减少,两组血管壁结构较清晰、少见内皮损伤,且SIM和XJP中剂量组的心肌细胞排列较整齐、少量心肌细胞肥大、变性等。结论临床等效剂量的XJP对大鼠高脂血症和脂肪肝具有明显的治疗作用,同时减轻血管内皮和心肌的损害,其作用机制可能与抑制HMGCR活性来降低胆固醇的生物合成、降低ACAT的活性及CETP的水平来增加脂质代谢转运有关。

OBJECTIVE To investigate the effects and mechanism of Xiongdan Jiuxin pills(XJP)on blood lipid,liver function vascular endothelial and heart in hyperlipidemic rats.METHODS The hyperlipidaemic rat model was developed by feeding rats with high fat diet(HFD).SD rats were randomly divided into HFD group,simvastatin group,low-,medium-and high-doses of XJP groups.After daily administration by gavage for 9 weeks,the levels of TC,TG,LDL-C,HDL-C,NO,ET-1,CETP and the activity of AST,ALT,HMGCR in serum,as well as the contents of TC,TG and the activity of ACAT in the liver were measured in rats.HE staining was used to observe the pathological changes of the liver,aorta and heart.RESULTS After 9 weeks of drug intervention,compared with the HFD group,the serum levels of TC,TG,LDL-C,ET-1,CETP and AST,ALT,HMGCR activity,and liver levels of TC,TG and ACAT activity were reduced to different degrees in XJP each dose group and SIM group,and the serum levels of HDL-C and NO were increased.In addition,pathological changes in the liver,aorta and heart were reduced to varying degrees in the drug-treated group,in which the liver cell structure was more intact and large vesicular lipid droplets were reduced in the SIM and XJPm groups,the vessel wall structure was clearer and less endothelial damage was seen in both groups,and the cardiomyocytes in the SIM and XJPm groups were more neatly arranged and a small number of cardiomyocytes were hypertrophied and degenerated.CONCLUSION Clinically equivalent doses of XJP showed significant therapeutic effects on hyperlipidaemia and fatty liver in rats,while reducing endothelial and myocardial damage.The mechanism might be related to the down-regulation of HMGCR activity to reduce cholesterol biosynthesis,reduce the ACAT activity and CETP level to increase lipid metabolism and transport.