The Preliminary Study On The Etiology And Pathogenesis Of Cholesterol Granuloma Media

Objective: Through analyzing the characteristics of lipid metabolism in the middle ear in patients with cholesterol granuloma,we aim to explore the relationship between cholesterol granuloma media and dyslipidemia.The study is designed to examine the expression of the NLRP3 inflammasome and its downstream protein Caspase-1 in patients with cholesterol granuloma and explore the significance of NLRP3 inflammasome in cholesterol granuloma,and provide a new clue for the study of the clinical prevention and treatment of cholesterol granuloma media.Methods: 1.Retrospective analysis of 57 cases of cholesterol granuloma media patients' serum triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL),high density lipoprotein cholesterol(HDL),APOlipoprotein A1(APOA1),APOlipoprotein B(APOB)content was conducted.And at the same time,57 cases of patients excluded cholesterol granuloma media with the pathological and imaging data from the similar age and gender were analyzed as the control.2.A total of 27 cases of patients with cholesterol granuloma were chosen as the case and 27 cases of patients excluded cholesterol granuloma media with the pathological and imaging data were analyzed as the control.The pathological changes and positive expression of NLRP3 and Caspase-1 in tissue were examined by HE staining,immunohistochemical staining and RT-qPCR method,and the data were analyzed.Results: 1.The levels of TC and LDL in cholesterol granuloma media group were5.09±1.13 and 2.91±0.81(mmol/L),and the levels in the control were 4.56±0.86 and2.51±0.58(mmol/L).The experiment group was higher than the control,and the difference was statistically significant(P<0.05).The level of APOA1 in the experimental group was 0.93±0.27(mmol/L),and the level in the control was1.03±0.26(mmol/L).The experiment group was lower than the control,and the difference was statistically significant(P<0.05).There was no significant difference in the levels of TG,HDL and APOB between the two groups(P>0.05).The levels of LDL/APOA1?APOB/APOA1 in the experimental group were 3.83±1.24 and 1.22±0.38,and the levels in the control were 2.56±0.81 and 1.37±0.39.The experiment group was higher than the control,and the difference was statistically significant(P<0.05).There was no significant difference in the levels of APOB and HDL/APOB between the two groups(P>0.05).The conditional Logistic multiple factors analysis showed that TC,LDL was the risk factor for cholesterol granuloma media.2.HE showed that there was a large amount of cholesterol crystals in the experimental group,surrounded by macrophages and inflammatory cells,while inflammatory cells were mostly neutrophils and a scatter of macrophages in control group.The results of immunohistochemistry showed that the expression of NLRP3 in the two groups was located in the cytoplasm,and the positive cells could be dyed yellow or brown granules.Compared with the control group,the staining intensity and expression number of NLRP3 in the cholesterol granuloma tissues were significantly increased.The positive rate of NLRP3 expression was 66.7%(18/27)in the experimental group.The positive rate of NLRP3 expression was 25.93%(7/27)in the control.The RT-q PCR detection showes that the expression of NLRP3 m RNA was 1.57±0.15,and the Caspase-1 m RNA was 1.35±0.17 in the experimental group.The expression of NLRP3 m RNA was 0.56±0.08,and the Caspase-1 m RNA was 0.40±0.09 in the control.The differences were also statistically significant(P<0.05).3.Pearson correlation analysis showed that the expression of NLRP3 was positively correlated with the Caspase-1 in the experimental group(r = 0.933,P<0.01)as well as in the control(r = 0.761,P<0.01).Conclusion: 1.Patients with cholesterol granuloma media's lipid levels are higher than the patients without cholesterol granuloma media,and TC,LDL,APOA1,LDL/APOA1 and APOB/APOA1 levels have correlation with the onset of the middle ear of cholesterol granuloma.TC and LDL levels are important risk factors for the onset of cholesterol granuloma in the middle ear.2.The level of NLRP3 and Caspase-1 expression in the experiment group is higher than the control,and the two factors are in positive correlation.This suggest that the NLRP3-Caspase-1 signaling pathway may be involved in the pathogenesis of cholesterol granuloma.