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Effect Of Chronic Intermittent Hypoxia On The Expression Of Mitochondrial Dynamin Proteins Fis1 And Mfn1 In Rats And Its Clinical Significance

Posted on:2020-10-31Degree:MasterType:Thesis
Country:ChinaCandidate:M T WangFull Text:PDF
GTID:2404330590456002Subject:Internal Medicine
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Objective:In this study,the rat model of CIH was used to simulate OSAHS.The effects of CIH on mitochondrial dynamics and its clinical significance were studied by measuring the expression of mitochondrial kinetics proteins Fis1 and Mfn1 in rat kidney.Whether the endogenous cannabinoids system?ECS?causes kidney damage by affecting mitochondrial dynamics were further studied.Methods:40 healthy adult male Sprague-Dawley rats were selected to establish a CIH model to simulate OSAHS.The rats were randomly divided into 5 groups,normal control group,CIH 4 weeks group,CIH 6 weeks group,CIH+drug intervention 4 weeks group,CIH+drug intervention 6 weeks group.The intervention group was intraperitoneally injected with rimonabant(CB1RR antagonist)1.5 mg/kg/d before the model establishment,and the other groups were given the same amount of normal saline.At the 4th week and the 6th week of the experiment,all the rats were sacrificed,and the kidney tissues of each rat were isolated and embedded in paraffin.The pathological changes of renal tissues were observed under light microscope after HE staining.The expression of Fis1 and Mfn1 in rat kidney tissues was detected by immunohistochemistry.Data were processed using SPSS 25.0 statistical software.One-way analysis of variance was performed using a completely randomized design.LSD-t test was used between groups to perform multiple comparisons between means.The meanąstandard deviation?<sub>xąs?was used to represent the count data.Results:1.Pathological changes of HE staining:There were no abnormalities in the morphology of glomerular and renal tubular epithelial cells in the control group.The renal tubular epithelial cells in the CIH 4 weeks group were moderately swollen,the cytoplasm was sparse,and the lumen was narrow.There was no obvious abnormality in the glomerulus;the tubular epithelial cells in the CIH 6 weeks group were disordered,the cytoplasm was particularly sparse,the swelling and degeneration were high,the lumen was narrowed and disappeared,the glomerulus was slightly swollen,and the balloon gap was mildly narrow;The renal tubular epithelial cells in the CIH+drug intervention 4weeks group were more neatly arranged and less swollen than the CIH 4 weeks group.The tubular epithelial cells in the CIH+drug intervention 6 weeks were less swollen than the CIH 6 weeks group.The degree of glomerular swelling was reduced and the balloon gap was slightly widened.2.Compared with the control group,the expression of Fis1 protein in renal tubular epithelial cells of CIH group was significantly increased,while the expression of Mfn1protein was significantly down-regulated,the difference was statistically significant?P<0.05?,among which CIH 6 weeks group The most obvious change was that Fis1 was positively correlated with CIH time,while Mfn1 was negatively correlated with CIH time.3.Compared with the simple CIH group,the expression of Fis1 protein in renal tubular epithelial cells was down-regulated and the expression of Mfn1 protein was up-regulated in the drug intervention group?P<0.05?.Conclusion:1.It was confirmed that CIH can induce changes in mitochondrial dynamics,and mitochondrial fission increased with the prolongation of CIH time;2.CB1 receptor antagonist?rimonabant?intervention can inhibit CIH-induced mitochondrial kinetic disorder,thereby reducing CIH-induced renal tissue damage in rats.
Keywords/Search Tags:Chronic Intermittent Hypoxia, Renal, Mitochondrial dynamics, Endocannabinoid System
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