The Effect Of Chronic Intermittent Hypoxia On Expression Of Renal Cohesive Protein P66Shc In Rat Model And Its Clinical Significance

Objective:To observe the pathological changes of rat kidney under CIH and CIH after intervention by CB_1RR antagonist rimonaban,and to explore the possible mechanisms of p66Shc and endocannabinoid system in CIH-induced renal injury by measuring the expression of p66Shc in kidney tissue;to preliminarily explore the correlation between p66Shc and endogenous cannabinoid system.Methods:Thirty healthy adult Wistar male rats were randomly divided into five groups:normal control group,4,6W hypoxic group（HI）,4,6W hypoxic intervention group,where the HI group were given intraperitoneal injection CB_1RR antagonist rimonaban with1.5mg/kg/d dose treatment.At 4 and 6 weeks,half of the rats in thehypoxic and intervention group were randomly sampled.Kidney tissues were collected after execution.The morphological changes of kidney tissues were observed under light microscope.The expression of p66Shc in kidneys of rats in each group was detected by immunohistochemical method.The data were expressed by grayscale and analyzed by SPSS25 software.Results:1.HE staining morphology of rats,kidney tissue from each group:（1）The renal tissue structure of the control group was normal,and the boundaries between the structures were clear and the staining were uniform.（2）Glomerulars swelling,mesangial mild hyperplasia,renal tubular epithelial cells highly swelling,lumen stenosis and brush border decreased or disappeared can be seen in IH group rats,kidney,in which the change of 6-week hypoxic group was more obvious than the 4-week hypoxic group.（3）The injury in IH+intervention group was reduced compared with the simple hypoxic group.2.Immunohistochemical expression of p66Shc:（1）Brown particle was observed in the cytoplasm of rats,glomeruli and tubule in each group,and the expression of p66Shc in renal tubule was dominant,especially in the proximal tubule.（2）The color of the control group was lighter than that of the simple hypoxic group,and the difference was statistically significant（p<0.05）.（3）Positive expression of p66Shc was significant in the simple hypoxia group,with the strongest expression in 6-week IH group,and the difference was statistically significant（p<0.05）.（4）The color of the intervention group at4 and 6 weeks was lighter than that of the simple hypoxia group at 4 and 6 weeks,and the positive expression of p66Shc was decreased in the intervention group,and the difference was statistically significant（p<0.05）.Conclusion:1.CIH can cause renal injury,and the degree of injury is proportional to intermittent hypoxia time;2.The increased expression of p66Shc in the renal tissue of CIH,especially in the proximal renal tubules,suggests that p66Shc may play an important role in cih-induced renal injury;3.The intervention of the CB_1RR antagonist rimonabant can improve renal injury,suggesting that ECs is involved in CIH renal injury;4.After the intervention of the CB_1RR antagonist rimonabant,the expression of adaptor protein p66Shc was down-regulated,suggesting that the endocannabinoid system may be the upstream regulatory system of p66Shc.