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CB1 Receptors In The Rat Model Of Chronic Intermittent Hypoxia Abnormal Bone Metabolism Mechanism Of Action

Posted on:2016-10-04Degree:MasterType:Thesis
Country:ChinaCandidate:Y L JiaFull Text:PDF
GTID:2284330479492458Subject:Internal medicine
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Objective:To observe the endocannabinoid system(ECs) in cannabinoid receptor 1(CB1R)situation and trend after the intervention CB1 R expressed in bone tissue,and by measuring the levels of bone-derived enzyme TRAP, Discussion After using CB1 R antagonist rimonabant intervention can alleviate bone metabolism and risk of abnormal bone structure in rats CIH.Methods:select 48 male SD rats, by establish the OSAS typical pathological model- chronic intermittent hypoxia(CIH) experimental animal models, according to the different methods of exposure and cycle times were randomly divided into six groups,namely4,6W hypoxic group(IH), 4,6W the control group(ON), 4,6W hypoxic intervention group(HI), where the HI group were given intraperitoneal injection CB1 R before modeling antagonist 1.5mg / kg / d were hypoxia treatment. In the experiment of 4W, 6W randomly selected half of the rats when the experiment was terminated, taken femoral vein 5ml, 1h standing later,centrifuged the supernatant to determine the serum TRAP content by using ELASA method; then intercept the bone tissue of rats in each group with decalcification solution soak until softened tissue, after paraffin embedding machine slicer cut in a uniform thickness of bone tissue placed on a glass slide, HE staining in light microscopy whether the change in bone microarchitecture; observe the expression of bone tissue CB1 R using immunohistochemistry and determination.Results:(1) TRAP determination: After modeling, 4W and 6W-IH group were higher than TRAP modeling before 4,6W-ON group, there was difference(t =-7.930, P <0.001), and Comparison between ON TRAP activity level group, the difference was not statistically significant(t =-1.273, P = 0.224); after the intervention, 4W and 6W-HI group TRAP levels were lower than before the intervention 4,6W-IH group, there are statistical difference(t =-7.930, P <0.001), these results prompted increased after hypoxia time TRAP levels can be elevated above normal, but after the intervention, TRAP levels can interfere with the extension of time gradually decreased, statistical significant difference(P <0.001).(2) Bone tissue HE staining: ON group showed morphologically normal bone cells were observed to maintain the integrity of the structure and the number of trabecular bone; 4IH group osteoblasts slight edema, the number of trabecular bone are missing, the structure has been destroyed; 4HI group morphological changes of bone, trabecular number and structural damage to a slight improvement, the above tips bone morphology between 4,6WON group, trabecular number structure did not change significantly, if the increase in hypoxia time, 6IH group of bone cells severe morphological changes compared 4IH, trabecular number and range of the previous extensive structural damage,and after increasing the intervention time, 6HI the group bone cell morphology and structural disorder degree of trabecular bone compared 4HI eased.(3) CB1 R expression in bone tissue: â‘  viewed from the microscopic to the expression of bone tissue ON group CB1 R located osteoblasts, osteoclasts and bone marrow stromal cells in the cytoplasm and nucleus. â‘¡ IH group was observed in positive osteoblasts CB1 R wide range of expression than the ON group, but after the intervention group CB1 R HI convey the scope of bone cells than lower IH group, the difference was statistically significant(P <0.001). No â‘¢ON group between the expression levels of bone cell CB1 R significant difference; prolonged hypoxia time, IH group CB1 R osteoblasts increased expression region; post-intervention time increases, reducing the HIgroup CB1 R expression levels, statistically significant(P< 0.001).(4) Correlation analysis: Pearson correlation analysis showed a positive correlation existed(between the expression of osteoclasts and osteoblasts CB1 R and bone metabolism markers TRAP activity levels,OC :r =0.836, P <0.001, OB: r = 0.806,P<0.001).Conclusion:The clear ECs disorder caused by abnormal occurrence and mechanism of action of CIH bone metabolism and bone structure concerned and give interventions before CIH after modeling, can effectively reduce the ECs and bone metabolism disorders occur, and with hypoxia extension of time, the expression of bone cells CB1 R, destruction of bone metabolic enzyme content and bone structure is also more serious, while the serum levels of TRAP expression of CB1 receptors line correlation analysis concluded that there is a positive correlation between the two, TRAP can be one indicator of the severity of bone metabolism as judged by OSAS trigger.
Keywords/Search Tags:obstructive sleep apnea syndrome, cannabinoid receptor 1, rimonabant, bone-derived acid phosphatase, chronic intermittent hypoxia
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