Effect Of Chronic Intermittent Hypoxia On The Structure Of Kidney,Matrix Metalloproteinase-1,8,9 And Tissue Inhibitor Of Metalloproteinase-1 In Mice

Objective: To explore the effect of chronic intermittent hypoxia(CIH), an important pathophysiological state of sleep apnea syndrome , on the renal structure and expression of matrix metal Loproteinases (MMPs) and tissue inhibitor of metal loproteinases (TIMPs) in mice kidneys. Methods: 30 1CR mice were randomly divided into four groups, control group (sham CIH, 10 mice)and three CIH groups ,which were exposed to intermittent hypoxia for 8 weeks(10mice),4 weeks (5mice) and 2 weeks (5mice) respectively. Each cycle of hypoxia-reoxygenation in CIH was 2 minutes. Hist.opathological method was applied to observe the renal structure and immunohistochemistry was used to detect the expression of MMP-1,8,9 and TIMP-1 in mice kidneys. Results: Pathological changes mainly appeared in proximal convoluted tubule. Swelling , vacuolar degeneration and granular degeneration were found in epithelial cells of renal tubule in the CIH groups and areas of degeneration were expanding when CIH continued. Necrosises were found in part of renal tubule of 8 weeks group. Invasion of noutrophils and macrophages were not found in each group. MMP-1, MMP-9 and TIMP-1 were mainly expressed in tubular cells. MMP-8 was not expressed. Compared with control group, the expressions of MMP-1 decreased significantly in three CIH groups (P<0.01). Expression of MMP-1 was lowest at two weeks, and increased slightly after that, but there were no significant differences among CIH groups (P>0.05) . Expression of TIMP-1 and MMP-9 in the two weeks group were both significantly higher than that of control group (P<0.01) , but kept decreasing with the prolong of CIH. Expression of MMP-9 in the four weeks group and the 8 weeks group were lower than that of the control group (P<0. 01), while...