| Objective:To investigate the effect of luteolin on blood lipid,hepatic steatosis and liver gene expression in hyperlipidemia SD rats and provide basis for the mechanism of luteolin on lipid metabolism.Methods:Forty male Sprague-Dawley rats were randomly divided into two groups.10 rats of normal control group were fed with D12450B diet and 30 rats of model group were fed with D12492 diet.After 4 weeks,fasting serum TG,TC of the model group rats significantly increased(P<0.05)were considered as the hyperlipidemia rats.Then 30 hyperlipidemia rats were randomly divided into model control group,luteolin intervention group and simvastatin control group.Normol and model control groups were both intragastrically administered with 0.5%sodium carboxymethylcellulose(CMC)solution at 10 ml/kg per day.The luteolin intervention group and simvastatin control group was intragastrically administered with 50 mg/kg luteolin and 10 mg/kg simvastatin daily for 6 weeks.The blood and some tissues were collected.(1)Liver,brown fat,testicular fat,perirenal fat,mesenteric fat,retroperitoneal fat were weighed and liver index,fat rate were calculated.Part of testicular fat was taken for HE staining and pathological changes were observed,serum TC,TG,HDL-C,LDL-C and apolipoproteins(Apo-A1,Apo-B)were detected.(2)HE staining was used to observe liver pathological changes,serum liver function indexes(AST,ALP,ALT)were detected,antioxidant indexes(SOD,GSH-Px,MDA,CAT),enzymes related with lipid metabolism(FAS,DGAT,HMG-CoA,APO,HL,CYP7A)in the liver were detected.(3)RNA of liver was extracted for whole-genome expression profiling.Gene Ontology and KEGG pathway were used for analyzing differential expression genes.Several genes related with lipid metabolism were selected for Real-timePCR(qPCR)verification.Results:(1)Compared with the normal control group,the weight,fat rate,liver index and serum TC,TG,LDL-C of the model control group were significantly increased(P<0.05),serum HDL-C,Apo-Al were significantly decreased(P<0.05),Apo-B was increased but not statistically different,volume and area of fat cell were increased;Compared with model control group,the weight,liver index,fat rate and serum TC,TG,LDL-C of luteolin intervention and simvastatin control group were significantly decreased(P<0.05),Apo-A1 was elevated and Apo-B was decreased but not statistically different,the volume and area of fat cells were decreased.Compared with the simvastatin control group,the general indicators,serum lipid and apolipoprotein levels of luteolin intervention group were not statistically different.(2)Compared with the normal control group,many lipid droplets were in the model control group(P<0.01),serum AST,ALP,ALT increased significantly(P<0.05),liver antioxidant enzyme CAT decreased and MDA significantly increased(P<0.05),FAS,DGAT and HMG-CoA were significantly increased(P<0.01),FA?O,HL and CYP7A were significantly decreased(P<0.01).Compared with the model control group,lipid droplets both in the luteolin intervention and simvastatin control group livers were decreased,the structure of the liver sinus was gradually clear,the serum ALP and ALT levels were significantly decreased(P<0.05),AST was decreased but not statistically different,liver antioxidant enzyme CAT increased(P<0.01)and MDA decreased significantly(P<0.05),the contents of FAS,DAGT,HMG-CoA were decreased and FA?O,HL and CYP7A were significantly increased in liver(P<0.05).Compared with the simvastatin control group,the MDA content of the luteolin intervention group was higher and the CAT content was lower but not statistically different the HMG-CoA was significantly decreased(P<0.01),the content of CYP7A was significantly increased(P<0.01).(3)Compared with the model control group,451 differential expression genes were shown in gene chip,of which 116 up-regulated and 335 down-regulated.68 differential genes were significantly concentrated both in GO and KEGG pathway.4 genes related to lipid metabolism were selected for qPCR verification.ACSL3 and DHCR7 gene expression were significantly decreased(P<0.05),and CYP7A1 gene expression was significantly increased(P<0.05).Conclusion:Luteolin can significantly improve the blood lipid,morphological changes of fat cells and hepatic steatosis in hyperlipidemia SD rats.Luteolin can improve the anti-oxidation level and lipid metabolism-related enzyme activities.Compared with simvastatin,it has no statistical difference in general obesity index,blood lipid level,histopathological changes,liver function and antioxidant level in hyperlipidemic SD rats,and the effect of regulating lipid metabolism-related enzymes in luteolin intervention group may be better.Luteolin may participate in cholesterol-bile acid conversion,cholesterol synthesis and cellular fatty acid uptake and other processes in liver of hyperlipidemic SD rats by regulating the expression of related lipid metabolism genes such as ACSL3,DHCR7,GPAM,CYP7A1.Luteolin can be further studied and developed as a novel lipid-lowering natural phytochemical. |
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