Abstract:[Abstract] Objective To investigate the effect of echinacoside (ECH) on liver lipid metabolism in db/db mice and its mechanism. Methods Twenty-one healthy male db/db mice aged 8 weeks and weighing from 40 to 48 g were divided into db/db+ECH group [n = 11, ECH, 300 mg/(kg·d)] and db/db group (n = 10, given the corresponding volume of saline) by random number table, db/m mice born with same littermates were served as normal control group, that was db/m group (n = 9, given corresponding volume of normal saline). The weight of the mice was measured weekly. The mice were sacrificed 10 weeks after the intervention. The liver tissues were sacrificed and the wet weight of the liver and the weight of the fat around the testes were measured. The total RNA of the liver was extracted and the mRNA of peroxisome proliferator-activated receptor α (PPAR-α) and carnitine palmitoyl transterase-1 (CPT-1) were detected by real-time quantitative PCR. Liver tissue hematoxylin-eosin (HE), oil red O staining were used to evaluate pathologic changes. The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured by automatic biochemical analyzer after fasting for 12 hours and 1 d before the rats were sacrificed. Results Compared with db/m group, the body weight, wet weight of liver and testicular fat around the weight in the db/db group were increased, and the levels of ALT, AST, TG, TC, LDL-C in serum were increased and HDL-C in serum was decreased (P < 0.05 or P < 0.01), liver tissue showed liver cell swelling, vacuolar degeneration, a lot of lipid deposition; ECH intervention could reduce body weight, liver wet weight and testicular fat around the weight of db/db mice, decrease the levels of ALT, AST, TG, TC, LDL-C and increase the level of HDL-C (P < 0.05 or P < 0.01), improve the pathological changes of liver tissue and lipid deposition, and up-regulate the expression of PPAR-α and CPT-1 in liver tissue (P < 0.05). Conclusion Echinacoside has protective effect on liver of db/db mice, and its mechanism may be related to up-regulating the expression of PPAR-α and CPT-1 in liver tissue and improving lipid metabolism.
[1] Perla FM,Prelati M,Lavorato M,et al. The Role of Lipid and Lipoprotein Metabolism in Non-Alcoholic Fatty Liver Disease [J]. Children(Basel),2017,4(6):46.
[2] Fan J,Li H,Nie X, et al. MiR-30c-5p ameliorates hepatic steatosis in leptin receptor-deficient(db/db)mice via down-regulating FASN [J]. Oncotarget,2017,8(8):13450-13463.
[3] 胡晓娜,周灿灿,保志军.非酒精性脂肪性肝病及肝细胞癌的相关性研究进展[J].中华消化杂志,2016,36(12):864-866.
[4] Tu PF,Wang B,Deyama T,et al. Analysis of phenylethanoid glycosides of Herba cistanchis by RP-HPLC [J]. Yao Xue Xue Bao,1997,32(4):294-300.
[5] 雷箴,温韬.松果菊苷对刀豆蛋白A所致急性肝损伤小鼠的保护作用及对细胞外组蛋白的影响[J].解放军医学杂志,2016,41(2):97-102.
[6] You SP,Ma L,Zhao J et al. Phenylethanol Glycosides from Cistanche tubulosa Suppress Hepatic Stellate Cell Activation and Block the Conduction of Signaling Pathways in TGF-beta1/smad as Potential Anti-Hepatic Fibrosis Agents [J]. Molecules,2016,21(1):102.
[7] 中华医学会肝病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南(2010年修订版)[J].中华肝脏病杂志,2010,18(3):163-166.
[8] Schmittgen TD,Livak KJ. Analyzing real-time PCR data by the comparative C(T)method [J]. Nat Protoc,2008,3(6):1101-1108.
[9] 范竹萍.非酒精性脂肪性肝病研究热点及防治管理[J].中华健康管理学杂志,2015,9(2):140-141.
[10] 郭凯锋,陈海冰.高尿酸血症、痛风与非酒精性脂肪肝的相关性研究进展[J].中华糖尿病杂志,2015,7(9):581-584.
[11] Tesch GH,Lim AK. Recent insights into diabetic renal injury from the db/db mouse model of type 2 diabetic nephropathy [J]. Am J Physiol Renal Physiol,2011,300(2):F301-F310.
[12] 徐磊,厉有名.过氧化物酶体增殖物激活受体α在脂肪性肝病发病机制中的作用[J].中华肝脏病杂志,2005, 13(9):715-717.
[13] Kallwitz ER,McLachlan A,Cotler SJ. Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease [J]. World J Gastroenterol,2008,14(1):22-28.
[14] Ip E,Farrell GC,Robertson G,et al. Central role of PPARalpha-dependent hepatic lipid turnover in dietary steatohepatitis in mice [J]. Hepatology,2003,38(1):123-132.
[15] Watts GF,Barrett PH,Ji J,et al. Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome [J]. Diabetes,2003, 52(3):803-811.
[16] Li F,Patterson AD,Krausz KW,et al. Metabolomics reveals an essential role for peroxisome proliferator-activated receptor alpha in bile acid homeostasis [J]. J Lipid Res,2012,53(8):1625-1635.
[17] Fraulob JC,Souza-Mello V,Aguila MB,et al. Beneficial effects of rosuvastatin on insulin resistance,adiposity,inflammatory markers and non-alcoholic fatty liver disease in mice fed on a high-fat diet [J]. Clin Sci(Lond),2012, 123(4):259-270.
[18] Souza-Mello V,Gregorio BM,Cardoso-de-Lemos FS,et al. Comparative effects of telmisartan,sitagliptin and metformin alone or in combination on obesity,insulin resistance,and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet [J]. Clin Sci(Lond),2010, 119(6):239-250.
[19] Everett L,Galli A,Crabb D. The role of hepatic peroxisome proliferator-activated receptors(PPARs)in health and disease [J]. Liver,2000,20(3):191-199.
[20] Vonghia L,Magrone T,Verrijken A,et al. Peripheral and Hepatic Vein Cytokine Levels in Correlation with Non-Alcoholic Fatty Liver Disease(NAFLD)-Related Metabolic,Histological,and Haemodynamic Features [J]. PLoS One,2015,10(11):e0143380.