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The Study on Anti-atherosclerosis Effect and Its Mechanisms of Housefly Maggot in ApoE-/- Mice

Author: XiaoMingZhu
Tutor: ZhuJiaYong
School: Guangdong College of Pharmacy
Course: Pathogen Biology
Keywords: Atherosclerosis Housefly maggot powder ApoE knockout mice Hypolipidemic Antioxidant
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 69
Quote: 0
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Abstract


Atherosclerosis (atherosderosis, AS) refers to the artery and its branches vessel wall intima and intimal lipid calm, accompanied by medial smooth muscle cell migration to endometrial proliferation to intimal thickening, formation of yellow shaped like a porridge-like substance or greyish plaque. Atherosclerosis can lead to cardiovascular and cerebrovascular disease, serious harm to human health. Of atherosclerosis and resulting cardiovascular and cerebrovascular disease incidence increased year by year, and the incidence was younger trend. Atherosclerosis has been important for the medical profession, but its therapeutic efficacy is limited and requires long-term use. Widely used in clinical anti-atherosclerosis drugs, such as the presence of simvastatin, probucol are the side effects can not be ignored, and its long-term efficacy in clinical highly questionable. So, looking for a natural, non-toxic, and effective anti-artery atherosclerosis drugs is one of the focus of clinical pharmacy. The housefly maggot (Housefly maggot, HM) contains a variety of bioactive peptides, has been proven to lower cholesterol, improve the immune capacity, lowering blood pressure and other effects. Since the 80s of the last century, Musca domestica, chitin and other biologically active substances has been one of the hot spots in the field of life science research. Our preliminary results show that the the housefly maggots powder can effectively reduce hyperlipidemia SD rats lipid levels, and SD rats atherosclerosis prevention. To further investigate the housefly maggot powder anti-atherosclerotic effect, the experimental mouse atherosclerosis model internationally recognized - ApoE gene knockout (ApoE - / - ) as the research object housefly maggots powder to explore, from lowering blood pressure, anti-oxidation, anti-atherosclerotic mechanisms. Research methods: 1 ApoE knock-out in addition to (in ApoE - / - ) mice were grouped and drug treatment: breed identification ApoE - / - mice, randomized, divided into model control group the a housefly maggot powder processing (8g/kg/day) group, simvastatin treatment (50mg/kg/day) group; in ApoE - / - mice C57BL/6J mouse genetic background, it set up a group of C57BL/6J mice to do the normal control. To investigate the mechanism of the housefly maggot powder antioxidant Antioxidants commonly used in clinical treatment of atherosclerosis drug probucol (30mg/kg/day) to set up a treatment group to do a positive reference. Each group of mice to gavage medication treatment, model control group and blank control group I intragastric saline treatment. 2 housefly maggot powder explore ApoE - / - mouse atherosclerosis prevention and treatment effect: each group of mice medication after 8 weeks of treatment, positive reference to simvastatin treatment group, percentage of the aorta and the abdominal aorta Oil Red O staining plaques were detected the tricuspid parts pathological slice Oil Red-O staining plaque area and aortic cross-section biopsy Elastin Van Gieson (EVG) staining of elastic fibers hyperplasia situation and statistical analysis of data. Housefly maggot powder anti artery atherosclerotic lipid-lowering mechanism of detection the group in ApoE - / - the mouse cholesterol (TC), triglyceride (TG) level: every 14 days to lipid-lowering effect of simvastatin treatment groups doing positive reference to observe the housefly maggot powder. Simultaneous determination of the mouse bile flow and bile acid content, and to detect the activity of HMG-CoA reductase, to explore the The housefly maggot powder anti artery atherosclerotic lipid-lowering mechanism. The housefly maggot powder anti arterial investigate the antioxidant mechanism of atherosclerosis: detect the ApoE - / - mice every 14 days of high-density lipoprotein (HDL), low density lipoprotein (LDL ) level, probucol treated group positive reference, observed housefly maggot powder antioxidant effect. Detected simultaneously at 8 weeks after treatment the mouse blood malondialdehyde (malonyldialdehyde, MDA) and oxidized low-density lipoprotein (Ox-LDL) level, and to detect mice tricuspid plaque macrophage cells specific protein expression MAC-3, and the distribution of macrophages to explore the The housefly maggot powder anti-artery atherosclerosis antioxidant mechanism and its correlation with macrophage migration. Results: 1. Housefly maggot powder explore ApoE - / - mouse artery atherosclerosis prevention and treatment effect: prevention trials, model control group and housefly maggot powder prevention group aorta and abdominal aortic arteries percentage of the average of the atherosclerotic plaque area there is a very significant difference (21.34%, 13.58%, P lt; 0.01) between the two groups in the heart of the tricuspid valve parts atherosclerotic plaque area average value there are also very significant difference (216,272.27 ± 28649μm2 131,998.17 ± 24165μm2, P lt; 0.01). Therapy trial, part of the aorta and the abdominal aorta artery model control group and the housefly maggot powder treatment group atherosclerotic plaque area percentage of the average there was a significant difference (22.53%, 15.91%, P lt; 0.01) between the two groups in the heart of the tricuspid valve parts atherosclerotic plaque area average there are also significant differences (283,423.83 ± 34649μm2, 236,272.2347 ± 36749μm2, P lt; 0.05). In addition, of ApoE - / - mouse aortic cross-section histopathology Elastin Van Gieson (EVG) the elastic fibers specific staining results show that the prevention and treatment of experiments in ApoE - / - the mouse aortic elastic fibers hyperplasia mitigation. 2. The housefly maggot powder anti hypolipidemic mechanisms of atherosclerosis explore: of housefly maggot powder processing group the TC levels far lower than those in the untreated control group, there was a significant difference (P lt; 0.01) close to simvastatin treatment group; of housefly maggot powder processing group TG levels relative to the model control group also reduced, there is a significant difference (P lt; 0.05). Of housefly maggot powder treatment group bile flow is increased and better than simvastatin treatment group, and a significant difference (86.15 ± 16.11μl / h 121.02 ± 15.76μl / h, P LT; 0.05), total bile acid (TBA) excretion increased and a significant difference (3.34 ± 0.68μmol / h, and 4.79 ± 1.39μmol / h, P lt; 0.05), HMG-CoA reductase activity is reduced and has a significant difference (P LT; 0.05). 3. Housefly maggot powder anti artery atherosclerosis antioxidant mechanism to explore: compared with the model group, housefly the maggot powder processing group gradually increase HDL levels, and maintained at a higher level in about 14 weeks, there is a very significant difference (P lt; 0.01); of housefly maggot powder treatment group LDL levels after administration has been effectively controlled, maintained at a lower level. Compared to the the the of housefly maggot powder treated liver homogenate MDA and Ox-LDL levels with the model control group there is a very significant difference (P lt; 0.01; P lt; 0.005), Ox-LDL decrease was even higher than probucol The test group. Immunohistochemical results showed that significantly reduced the number of macrophages housefly maggot powder treated plaque. Conclusion: 1. Of housefly maggots powder ApoE - / - mouse artery atherosclerosis mitigation. Performance housefly maggot powder were reduced in ApoE - / - mouse aorta and abdominal aorta parts and tricuspid arteries porridge-like plaque area; Meanwhile, the ApoE - / - mouse aortic elastic fiber hyperplasia significantly alleviated. Housefly maggot powder anti-atherosclerosis effect involving lipid decline, its mechanisms and bile flow increased synthesis of total bile acid (TBA) promote the body cholesterol discharged accelerated and the rate-limiting enzyme in cholesterol synthesis system (HMC-CoA) related inhibition. 3 The housefly maggot powder anti atherosclerosis effect relates to the anti-oxidation effect, and its mechanism, and HDL levels increased to protect the LDL is not oxidized to Ox-LDL, reduces the oxidative stress of the body to reduce the Ox-LDL generating, macrophages migration of cells to the blood vessel wall by inhibition of to slow bubble lipid plaque formation and other related.

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