人参皂苷Rg1通过调节脂肪代谢改善非酒精性脂肪肝病大鼠的肝功能

Ginsenoside Rg1 improves liver function by regulating fat metabolism in rats with non-alcoholic fatty liver disease

目的:研究人参皂苷Rg1对高脂饮食(HFD)诱导的非酒精性脂肪肝病(NAFLD)大鼠肝脏β-氧化的作用。方法:60只SD大鼠随机分为对照组(CON)、HFD组、人参皂苷Rg1低、中、高剂量干预组(LDG、MDG及HDG)及阳性药物熊去氧胆酸钠治疗组(PDT)。HFD 8周后成功复制NAFLD模型,之后用相应药物治疗,治疗4周和8周后分别处死大鼠各半,收集肝脏做切片HE染色,同时检测其肝功能和血脂指标,RT-PCR及Western blotting测定肝脏脂酰Co A合成酶1(Co ASH1)、肉毒碱脂酰转移酶I(CATI)及脂酰Co A氧化酶1(ACOX1)mRNA和蛋白的表达。结果:治疗4周后,肝脏HE染色除HDG组有改善外,PDT组、LDG组及MDG组的脂肪肝浸润现象没有改善;治疗8周后,PDT组与LDG组仍有少量脂肪颗粒聚集,而MDG组和HDG组则看不到脂滴浸润现象;治疗4周后,PDT组、LDG组、MDG组及HDG组与HFD组相比,肝功能指标AST、ALT、AKP以及血脂指标TC、TG、LDLC明显降低(P<0.05),治疗8周后进一步降低;治疗4周后,4个治疗组HDL-C均明显升高,8周后几乎恢复到CON组的水平;治疗4周后4个治疗组肝脏组织的Co ASH1、CACTI及ACOX1表达均有显著升高(P<0.05),治疗8周后改善更为明显,同时MDG组与HDG组表达要高于PDT组(P<0.05)。结论:人参皂苷Rg1可通过调节大鼠β-氧化相关的酶改善脂肪代谢对NAFLD大鼠的肝损伤,从而发挥治疗作用。

AIM：To investigate whether ginsenoside Rg1 attenuates high-fat diet （ HFD）-induced non-alcoho-lic fatty liver disease （ NAFLD） by improving β-oxidation.METHODS： SD rats （ n=60） were randomly divided into control group （ CON ） , HFD group, low-dose, medium-dose and high-dose ginsenoside Rg1 groups （ LDG, MDG and HDG） and positive drug （ sodium ursodeoxycholate） treatment group （ PDT） .High-fat diet was given for 8 weeks to suc-cessfully establish an NAFLD model.The animals were treated with the appropriate medications for 4 weeks and 8 weeks af-ter modeling, and sacrificed to collect the liver tissues for observing the pathologic changes with HE staining and for detec-ting liver functions and lipid levels.The expression of hepatic acyl-CoA synthetase 1 （CoASH1）, carnitine acyltransferase I （CATI） and acyl-CoA oxidase 1 （ACOX1） at mRNA and protein levels was determined by RT-PCR and Western blot-ting.RESULTS：After 4-week treatment, the fatty infiltration of the liver tissues in PDT group, LDG group and MDG group was not attenuated except HDG group.After 8 weeks of treatment, a small number of fat particles was observed in PDT group and LDG group, while no infiltration of lipid droplet was found in MDG group and HDG group.Compared with HFD group, the levels of AST, ALT, AKP, TC, TG and LDL-C were significantly decreased after 4-week treatment in PDT group, LDG group, MDG group and HDG group （P〈0.05）, these indexes were further reduced after 8-week treatment. After 4-week treatment, HDL-C was significantly increased in the 4 treatment groups and almost restored to the level of＆nbsp;CON group after 8-week treatment.The levels of CoASH1, CACTI and ACOX1 in the liver tissue of the 4 treatment groups were significantly increased after 4-week treatment （P〈0.05） and much improved after 8-week treatment, and those in MDG group and HDG group were better than those in PDT group （P〈0.05）.CONCLUSION：Ginsenoside Rg1 regulatesβ-oxidation-related enzymes to improve the fat metabolism, thus playing a therapeutic role in liver injury in the rats with NAFLD.