| Objective:To observe the role of NLRP3 inflammasome mediated inflammatory response in liver injury and lipid metabolism abnormality in mice with nonalcoholic steatohepatitis and explore the related mechanism.Methods:8-week-old C57 BL / 6J male mice were randomly divided into normal group(n=10)and model group(n=10).NLRP3 gene knockout mice were used as experimental group(n = 10).The normal group was fed with normal diet for 16 weeks,and the model group and experimental group were fed with high fat and cholesterol diet for 16 weeks.The body weight,general condition and liver appearance of the three groups were recorded.The wet weight of liver and fat around epididymis were measured,and the liver index and fat index were calculated.The pathological changes of liver tissues were observed by HE staining,and the protein expressions of NLRP3,pro-caspase-1,IL-1β,SREBP-1 and SCD1 were detected by western blot.Results:1.Body weight,liver wet weight,liver index,epididymal fat weight and fat index of mice in each group: the weight,liver wet weight,fat weight,liver index and fat index of model group were higher than those of normal group,with significant differences(P = 0.001,0.000,0.001,0.025,0.001,0.001);the weight,liver wet weight,fat weight and fat index of experimental group were lower than those of model group,with significant differences(P = 0.034,0.001,0.000,0.00)There was no significant difference in liver index(P = 0.235).2.Liver histology of mice in each group: the scores of steatosis,ballooning degeneration,lobular inflammation,activity and fibrosis in the model group were higher than those in the normal group(1.86 ± 0.69 vs 0.00 ± 0.00,P = 0.001;1.71 ±0.49 vs 0.86 ± 0.38,P = 0.002;2.29 ± 0.76 vs 0.71 ± 0.48,P = 0.001;4.00 ± 0.63 vs1.57 ± 0.43,P = 0.000;1.13 ± 0.64 vs 0.00 ± 0.00,P = 0.002)The experimental group had significantly lower steatosis,ballooning degeneration,lobular inflammation and activity than the model group(1.14 ± 0.69 vs 1.86 ± 0.69,P =0.025;1.2 ± 0.58 vs 0.86 ± 0.38,P = 0.023;1.63 ± 0.53 vs 2.29 ± 0.76,P = 0.031;2.33 ± 0.56 vs 4.00 ± 0.63,P = 0.008);while the fibrosis stage score decreased,but the difference was not significant(1.13±0.64vs1.00±0.63,P = 0.758).3.Results of Western blot in liver tissue of mice in each group:the expression levels of NLRP3,pro-caspase-1,IL-1β,SREBP-1 and SCD1 in the model group were higher than those in the normal group(0.6428 ± 0.0859 vs 0.5003 ± 0.01,P = 0.026;0.9707 ± 0.022 vs 0.6408 ± 0.013,P = 0.041;1.3203 ± 0.0192 vs 0.2238 ± 0.025,P= 0.000;0.6556 ± 0.0585 vs 0.5392 ± 0.0534,P = 0.048;0.5994 ± 0.016)The expression levels of NLRP3,pro-caspase-1,IL-1β,SREBP-1 and SCD1 in the experimental group were significantly lower than those in the model group(0.3670± 0.056 vs 0.6428 ± 0.0859,P = 0.001;0.6995 ± 0.035 vs 0.9707 ± 0.022,P =0.049;1.2442 ± 0.0627 vs 1.3203 ± 0.0192,P = 0.049;0.5197 ± 0.0599 vs 0.6556 ±0.0585,P = 0.027;0.4955 ± 0.0519 vs 0.5994±0.0169,P=0.021).Conclusions:1.NLRP3 inflammasome mediated inflammatory response plays an important role in NASH mice liver injury and abnormal lipid metabolism,which may be related to the regulation of NLRP3—caspase-1—IL-1β and SREBP-1—SCD1 pathways;2.NLRP3 gene knockout can improve liver wet weight,fat weight and pathological changes in NASH mice;3.NLRP3 is expected to become a key target for NASH therapy. |
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