| BackgroundHyperlipidemia is currently considered to be one of the most important cardio-cerebral vascular disease risk factors. Cardiovascular disease is the main cause of death in developed countries, Although the pathogenesis has not been fully clarified, it is now widely recognized to be closely related with elevated blood lipids. Lipids mainly refers to the serum cholesterol and triglycerides. Hyperlipidemia refers to either or both of increasing levels of cholesterol or triglyceride.Hyperlipidemia can be divided into primary and secondary categories. Primary, hyperlipidemia is congenital and genetic related. It is due to single-gene or multiple gene defects, which result in abnomity of transport and metabolism of lipoprotein receptors, enzymes, or apolipoprotein caused by or due to environmental factors (diet, nutrition, drugs) and any unknown mechanism of Er Zhi. Secondary hyperlipidemia are mostly secondary to multi-secondary metabolic disorders (diabetes, hypertension, myxedema, hypothyroidism, obesity, liver and kidney disease, adrenal cortex hyperfunction), or other factors (age, sex, season, alcohol consumption, smoking, diet, physical activity, mental stress, emotional activity).The treatment for hyperlipidemia currently are oral drug therapy, Chinese medicine treatment, diet therapy and exercise therapy. All of the existing traditional drug treatment seem to be inefficacy. Therefore it is necessary to find drugs with better effect, fewer side-effects. Therefore, how to control hyperlipidemia has become an important research topic at home and abroad.Recently, many studies have shown that many active ingredients in crude chemicals have stable efficacy in prevention and treatment of hyperlipidemia, and with less toxicity and fewer adverse reactions, which can be made long-term use of. Among these, the chitosan and its derivatives with its unique physical and chemical properties has been research hotspot of the world since 1980s, and made big progress in medicine, food, chemical, environmental protection, agriculture and many other fields.Chitosan is a deacetylation product of chitin, which is a kind of natural polysaccharide. Its scientific name is poly glucosamine, which is also known as shell polyamines, and is the most fundamental and important derivatives of Chitin. It is first discovered by Rouget in 1859 in France. Chitosan with positively charged is rare in nature, it contains free amino, belongs to alkalinity polysaccharide, and its relative molecular mass, range from the hundreds of thousands to millions. This kind of polysaccharides can be biosynthesized, and also can be biodegradable, and have good biocompatibility with animal organs and cells, non-toxic. The low molecular weight oligosaccharide which produced during the process of degradation does not accumulate in the body.It also with no immunogenicity. Chitosan and its derivatives which is known to us have the pharmacological activities of lowering the blood glucose, anti-oxidation, anti-microbial, and enhance immunity, regulating blood lipids, inhibit tumor, and so on.Flyblow chitosan has its own unique advantage in the treatment of diabetes, its treatment of diabetes does not only including lowering the blood glucose simply, but also can improve lipid metabolism, correct the disorders of energy metabolism, improve the microcirculation, and protect pancreatic islet cells and tissue.It can prevent and cure the occurrence and development of the complications of diabetes which possess the value of exploitation and application.With the more in-depth studies on the mechanism of its anti-diabetic function,flyblow chitosan will play a greater role in the field of the treatment and prevention of diabetes.In this study, in accordance with the characteristics of the nutrition metabolism of hyperlipidemia, we establish a stable model of hyperlipidemia rats with regard to study the function of flyblow chitosan in regulation of lipidemia in order to lower the lipidemia. We use research tools of biochemistry and molecular biology, and incisivus from the view of Clinical Nutrition. This article focus on the phenomenon of regulating the metabolism of lipidemia enhance gastrointestinal motility, etc. to preliminary approach the mechanism of preventing hyperlipidemia function of flyblow Chitosan. This study provides new experimental evidence in order to prevent and cure hyperlipidemia and its complications, improving the quality of life of hyperlipidic patients. The study includes five parts:Research contentsPart One Experimental rat model of hyperlipidemiaObjective:To establish suitable experimental hyperlipidemia rat animal model successfully for nutritional therapy study. The model should be stable, reliable and repeatable.Method:20 Sprague-Dawley rats were randomly assigned into normal control group (n=10), and model group (n=10). High-fat feed is formulated with 1% cholesterol,10% lard, 10% egg yolk powder,0.2% bile salts, and 78.8% basic feed. After 1 week of adaptive feeding and 12h fasting (except for water), post-orbital venous plexus blood was collected. With 3000 r/min centrifugation 5 min, the serum was separated and 4 indexes about lipids were analyzed using biochemical analyzer, that is total cholesterol (TC), glycerol three esters (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). The normal control group are feed with the basic feeding fodder; the model group are fed with high fat diet feeding. After continuous feeding for 8 weeks and 12 h fasting, post-orbital venous plexus blood was collected. With 3000 r/min centrifugation 5 min, the serum was separated and 4 indexes about lipids were analyzed using biochemical analyzer,Result: before experiment, there were no significant difference in body weight of rats in each group (P> 0.05). After 8 weeks, weight of rats in model group feeding with high-fat feeding increased significantly compared with the normal control group, the difference was statistically significant (P<0.01). Serum TC, TG, LDL-C in hyperlipidemia model group increased significantly, and HDL-C decreased significantly, indicating that high-fat model modeling was successfully built.Part Two The effect of flyblow chitosan on lipid metabolism in experimental hyperlipidimia ratsObejective:To evaluate the effect of flyblow chitosan on lipid metabolism through several indexes as serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipase (LPS), free fatty acids (NEFA), hepatic lipase (HL), lipoprotein lipase (LPL) of experimental hyperlipidimia rats in order to study its mechanism in prevention and cure hyperlipidimia lesions.Method:70 Sprague-Dawley rats were randomly assigned into normal control group A (n=12) and hyperlipidemia model group (n=52) which modeling according to the method of part one.52 rats in hyperlipidemia model group that establish experimental hyperlipidemia model successfully randomly divided into B:model group (n=13), C low-dose group of flyblow chitosan (n=13); D:middle-dose group of flyblow chitosan (n=13); and E:high-dose group of flyblow chitosan (n=13).Intragastric administration to each group for 30 days, the doses are as follows:group A and group B intragastric administration with distilled water once a day; group C, D and E administratered one time a day with the dose of 160mg/kg·bw,320mg/kg·bw and 480 mg/kg·bw.After abrosiaing for 12h on the 31st day, post-orbital venous plexus blood was collected, total cholesterol (TC), glycerol three esters (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were tested. The rat would be anatomized. Body fat ratio, LPS, NEFA, HL, LPL and total lipide enzyme were tested.Results:Flyblow chitosan significantly reduce serum TC, TG, LDL-C, ALT, AST levels, increased HDL-C levels and reduced in each group; level of NEFA is significantly lower in Flyblow chitosan group than in model group and normal control group, and function of LPL and HL higher.there is no significant difference about LPS. The results showed that Flyblow chitosan is benefit for improving lipide metabolism abnormality of hyperlipidemia rats.PartThree The effect of flyblow chitosan on lipometabolic in experimental diabetic ratsObjective:to explore the mechanism of reducing blood glucose and improving lipide metabolism of flyblow chitosan by testing glucose glycated hemoglobin, serum.Method: biochemical analysis using glycosylated hemoglobin and serum insulin. Monitoring indicators are as follows: 1,fasting blood glucose on the 1d, 11d,21dand31d 2,glycosylated serum protein; 3,serum insulin.Results:after treatment of flyblow chitosan, fasting blood glucose of experimental hyperlipidemia in three experiment groups were significant lower compared with the model. glycosylated serum protein content in low, medium-dose group were lower than in the model control group, but there was no statistical significance. there was statistically significant difference between high-dose group and model control group (P<0.05); and compared with the model control group, insulin levels in low, medium, high-dose groups decreased in varying degrees.Part Four The effect of flyblow chitosan on gastrointestinal motility in experimental hyperdemia ratsObjective:To study on the gastrointestinal motility of experimental rats in order to determine the gastrointestinal transfer index, and approach the flyblow chitosan's mechanism of reducing complications and lowering blood lipid through improving intestinal function.Method:To calculate the gastrointestinal transfer index through measuring the total length of the small intestine of the experimental rats and the length of small intestine that traversing by Azovan Blue solution 30 min after intragastric administration.Results:The gastrointestinal transfer index of flyblow Chitosan treatment has significant difference (P<0.05) compared with the model group, among them, the middle-dose and the high-dose group had highly significant difference (P<0.01)This indicates that flyblow chitosan has a role of regulating the gastrointestinal function for experimental hyperlipidemia rats, and can stimulate enterokinesia, promote intestinal movement, so as to improve the condition of gastrointestinal dysfunction.Conclusions1. The experimental hyperlipidemia rat model can be successfully set up by feeding high fat diet for 8 weeks. This kind of hyperlipidemia model is suitable for the study of hyperlipidemia because the successful rate of model established is higher, the mortality rate is lower, and the symptom is stable.2. The typical symptoms of hyperlipidemia such as general physical condition, body weight, TC, TG, LDL-C, ALT, AST have improved after the treatment of flyblow chitosan. This indicated that flyblow chitosan has therapeutical effect for the treatment of hyperlipidemia.3. NEFA content in liver and adipose tissue in group with treatment of Flyblow chitosan is lower than model group and normal control group, and LPL and HL activity higher, suggesting that Flyblow chitosan can protect the liver cells, increased hepatic lipase and lipoprotein lipase activity, promote the body's fat metabolism and cholesterol metabolism, to stabilize the body's lipids.4. Flyblow chitosan can significantly improve glucose metabolism in rats with hyperlipidemia disorder, increase insulin sensitivity and improve insulin resistance, in order to decrease blood glucose and improve blood lipid lowering effect.5. Flyblow chitosan have a regulatory role in gastrointestinal disorders in hyperlipidemia, it can stimulate the intestinal peristalsis, promote bowel movement, thus improving the diabetic gastrointestinal dysfunction. It is maybe one of the mechanisms in improving the symptoms of hyperlipidemia. |
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