High-calorie feed for establishing atherosclerotic animal model and application thereof

Medicilon is a Preclinical Research Outsourcing (CRO) company. With our more than 10 years experience on preclinical research services, we dedicated to provide our clients with customized preclinical services program in drug metabolism, pharmacokinetics, efficacy studies, and toxicology. We provide our clients a high-quality data and rapid turnaround time to support their drug development, preclinical studies and clinical research and to help them to select the most valuable drug candidates into clinical trials stage. Our preclinical research services consist in three major parts: pharmacokinetics, disease transplantation models and drug safety evaluation. Our services cover all of the aspects including design, in vivo studies, sample analysis, professional data analysis, IACUC review, and the preparation of application materials.Email:marketing@medicilon.com.cn WEB:www.medicilon.com

The present invention discloses a method for establishing atherosclerosis in animal models of high-calorie diet and its application. The mass percentage of protein in feed for 18-20%, the percentage of fat mass 6-8%. The low-fat diet and cholesterol-free proportion of high-calorie recipes, modeling method is more moderate, not only in line with animal welfare, better simulation of atherosclerotic vascular damage sick people's eating habits, more conducive to disease and drugs the study. In the high-calorie diet prolonged chronic induced atherosclerosis model, more in line with human illness age group signs situation and eating habits, and human pathogenesis closer, the modeling process is more relaxed, more stable model. Can be used as lipid-lowering and anti-atherosclerosis ideal animal model studies of new drugs medicine services in preclinical research and drug evaluation.

The present invention belongs to the field of biology, it relates to an established animal model of atherosclerosis, high-calorie diet and its application. BACKGROUND:Atherosclerosis is cholesterol and cholesterol ester as a main component of lipids in the artery and its branches in the arterial wall intima or intima calm down, accompanied by medial smooth muscle cell migration to the subintimal hyperplasia, the inner membrane thickening, formation of atherosclerotic plaques yellow or brownish, causing vascular injury. Cause of atherosclerosis can be divided into internal external. Internal genetic factors, such as familial diabetes, coronary heart disease, as well as the sex and age factors: With age, the speed of the formation of atherosclerosis also accelerated. In terms of gender, women before menopause ovarian hormones protected, rarely atherosclerosis. There are external factors such as high blood pressure, high cholesterol, smoking, obesity, exercise too little, psychological stress and diabetes.

With the development of the social economy and increasing people's living standards, cardiovascular diseases and metabolic diseases such as hypertension, diabetes and high cholesterol has become the biggest killer of people's health. Among them, the death toll of cardiovascular disease every day worldwide due to hyperlipidemia caused nearly as many as 3600, China's annual high blood pressure due to high cholesterol caused by cerebral infarction, stroke, myocardial infarction, paralysis, disability, deaths annually increasing rise rate of 12%. And there is a Subsidiary show, high cholesterol, high blood sugar and insulin resistance can increase the risk of atherosclerosis. In recent years, atherosclerosis incidence by age of the elderly to young direction, and the incidence is increasing. Youth is the main force in the construction of national harmony, the mainstay of the community. The incidence of atherosclerosis caused annually to national and household huge economic losses, it has caused the medical and health sector and the national center of attention.

national "five" New Research Projects guide new drug research and development of key technology research Gui Gui expressly written: R & D needs to be complex diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and other drugs for the prevention and treatment of multifactorial Advantech traitor and a more sensitive, more reliable, more efficient new technologies and new models of early medicine evaluation, the evaluation group of innovative drugs varieties. But because of differences in species, the traditional laboratory animals such as small animals and rodent models currently widely used as an evaluation study based on the object of new drugs, it is far from normal human physiological indicators, a stable animal model has a similar pathogenesis of Establishment and Validation and Clinical vary. And pharmacokinetics of traditional animal experiments in rodents as kinetic objects obtained experimental results pharmacodynamic and safety of limited significance for clinical use, resulting in spending a lot of study based fee, but not the drug through clinical clinical trials or after the application of serious adverse reactions and endanger the lives of drug crowd.

In the non-human primate species rhesus study based on the object as the establishment of an appropriate animal model for screening new drugs, PK / ro traitor research and clinical drug trials before major significance. This is due to the similarity of nonhuman primates and human physiological structure, function and related indicators of disease diagnosis and treatment. The results of drug effects on non-human primates and get better conversion, clinical research traitor. Therefore the establishment of a non-primate animal model of atherosclerosis model become the treatment of a Subsidiary preclinical research drug evaluation urgent need.

However nonhuman primate model of atherosclerosis is usually a long period there is modeling, model lacks stability, the establishment of relevant platform model and the diagnosis and treatment technology, build technical difficulties such as incomplete. Jieyou abroad or patent coverage. Kukreja, R • etc. (Atherosclerosis, 1981. 40 (3):.. P 291-298) using 18 male and female of 2. 5-5 5kg weight of adult rhesus monkeys as modeling objects, feeding formula 15% protein, 15% fat, 60% carbohydrates, 1% cholesterol, coupled with the injection 50mg / kg per day the amount of adrenaline. Seven months after the killing of animals taken by pathological examination, we found 15 rhesus monkeys appear significant aortic and coronary atherosclerotic fibrous plaque. This method of drug intervention acute modeling, there is a certain model instability. Rhesus selected weight range does not belong to atherosclerosis weight range of vulnerable groups, not better simulate human pathogenesis. Detection method is invasive, is not conducive to applications and drug development model. There are both domestic use and rhesus monkey made cynomolgus reported hyperlipidemia and atherosclerosis model, the choice of feed formulation for the egg yolk powder 5%, 15% lard and cholesterol 0.5%, 75 basis feed %, modeling three months, and finally with TC, TG, and LDL-C to evaluate and confirm the model. Also belonging to acute modeling, high total cholesterol detrimental to animal health, and to lipid biochemical indicators to characterize atherosclerosis, convincing enough.

In summary, the existing non-human primate model of atherosclerosis, mostly through short-term high-cholesterol diet-induced acute obtained modeling methods to animal stimuli too intense, the model is not stable enough, and the real Atherosclerosis clinical manifestations are also quite different. Thus limiting the use of such animal models.

Therefore, the use innate obesity, aging populations in non-human primates such as the study based on an individual susceptible objects, fully simulate sick people diet, a high calorie diet diet for a long time as a method to establish a non-human-induced primate model of atherosclerosis, compared with short-term model of acute high-cholesterol diet-induced obtained modeling method is more peaceful, more stable model, in terms of genetics, cardiovascular function and lipid metabolism similar to humans. Currently the most commonly used clinical blood biochemistry is assisted Doppler ultrasound and magnetic resonance imaging (MRI) and other non-invasive imaging method to confirm the diagnosis of atherosclerosis. Thus, by Doppler ultrasound and non-invasive detection 3. OT MRI, etc., it can be more objective evaluation of the degree of atherosclerosis development and occurrence site. Since the detection method is non-invasive, stable model can be further used for the development of lipid-lowering and anti-atherosclerosis drugs.