Cholesterol-regulating Effects And Potential Mechanisms Of Chitooligosaccharide Capsules And Tablets In Hyperlipidemic Rats

Hyperlipidemia(HLP)is an important risk factor for the development of atherosclerosis and cardiovascular disease,and it is one of the most serious diseases in humans.At present,in the clinical treatment of HLP,chemical synthesis of lipid-lowering drugs accounted for the vast majority,but most of them are accompanied by serious adverse reactions.Therefore,it is of great significance to study the natural auxiliary hypolipidemic products which starting from the source and focusing on prevention with good efficacy and no toxic to reduce the incidence of dyslipidemia.Chitosan oligosaccharides(COS)is a degradation product of crustaceans such as shrimps and crabs.It is the only positively-charged cationic basic amino oligosaccharide in nature.Our group had previously prepared chitosan oligosaccharides(COST)of specific molecular weight and in vitro experiments have confirmed that COST can effectively inhibit the differentiation of 3T3-L1 preadipocytes,and significant inhibition of lipid accumulation in HepG2 cells;and COST is made into capsules(COSTC)and tablets(CFTs)by wet granulation and film coating technology which solved the problem of COST's hygroscopic deliquescence and browning.Based on the above experimental basis,this study established a HLP rat animal model induced by high-fat diet,and studied the functional activities of COSTC and CFTs in the body to help reduce blood lipids and its mechanism of lowering blood lipids.Cholesterol-regulating Effect studies have shown that COSTC and CFTs can demonstrate their hypolipidemic function through the following aspects:(1)COSTC and CFTs can significantly reduce the levels of TC,TG and LDL-C content,increase HDL-C content,and improve blood lipid level in HLP rats.(2)COSTC and CFTs could significantly increase TC,TG and TBA contents in the excrement of HLP rats and decrease the lipids in the liver of HLP rats And increase their lipid excretion into TBA after excretion and improve the HLP rat liver cholesterol by reverse transport and other indicators,thus minimizing the occurrence and development of fatty liver;(3)COSTC,CFTs has no toxic and side effects on the kidneys,liver and from the liver histomorphology and liver tissue sections results showed COSTC,CFTs have a certain effect of liver and liver protection;(4)COSTC and CFTs can reduce the body weight,body fat ratio,Lee's index,organ index and other obesity-related risk factors in a dose-dependent manner without affecting the appetite of HLP rats,and can inhibit the growth of rat adipocytes,and showed some weight-loss function.Compared with HF group,the number of significant genes up-regulated by COSTC was 113 and the number of significant genes was down-regulated by 517.The number of significant genes up-regulated by CFTs was 176 and the number of significant genes was down-regulated by 164.And GO function classification of differential genes was statistically analyzed,the differential genes are mainly distributed in the ribosomes,mitochondria,lysosomes,molecular functions involving the steroid binding,oxidoreductase activity,steroid dehydrogenase activity aspects;pathway significant enrichment pathways involved in lipid metabolism,steroid metabolism and steroid metabolism and other access.Results of cholesterol-regulating effects mechanism showed: COSTC,CFTs can increase the mRNA and protein expression of CYP7A1,LXRA,LDLR,PPAR? and reduce the mRNA and protein expression of SREBP2,HMGCR,thereby inhibiting the synthesis of cholesterol and promoting the cholesterol excretion.This research found will provide important theoretical supportd to development of COST-related hypolipidemic health products or Traditional Chinese Medicine five cholesterol-regulating drugs.