Objective: To investigate the curative effect and mechanism of hyperbaric oxygen therapy on nonalcoholic fatty liver disease in mice. Methods: Twenty-one 8-week-old male C57BL/6J mice were divided into three groups: control group (normal diet), model group (high-fat and high-cholesterol diet), and hyperbaric oxygen group (high-fat and high-cholesterol diet + hyperbaric oxygen therapy), with seven mice in each group. The changes in body weight, serum liver enzymes, and blood lipids were compared after treatment between the three groups. Hematoxylin-eosin staining, Oil Red O staining, Sirius red staining, and F4/80 immunohistochemical staining were used to observe the pathological changes in liver tissues. RT-qPCR and Western blot methods were used to detect the expression levels of oxidative stress and inflammatory factors. One-way analysis of variance was used for comparison among the groups. Results: Mice in the hyperbaric oxygen group had significantly improved liver histopathology. The serological levels of alanine aminotransferase, aspartate aminotransferase, and cholesterol were (77.50±13.59) U/L, (156.06±23.68) U/L, and (4.80±0.53) mmol/L, which were significantly lower than those in the model group [(109.43±16.88) U/L, (216.62±18.79) U/L, and (5.86±0.53) mmol/L, P<0.05], and accompanied by lower levels of lipid deposition, macrophage infiltration, and fibrosis. In addition, compared with the model group, the expression of antioxidant stress protein nuclear transcription factor erythroid 2-related factor 2 [(0.30±0.06) and (2.16±1.21), P<0.05] and heme oxygenase-1 [(0.48±0.19) and (1.01±0.18), P<0.05] in liver tissue showed an upward trend following hyperbaric oxygen treatment, which was also validated at the transcriptional level (P<0.05). Simultaneously, compared with the model group, the mRNA expressions of tumor necrosis factor-α [(2.60±0.71) and (0.66±0.15), P<0.05], interleukin-1β [(2.41±1.01) and (0.78±0.23), P<0.05], and interleukin-6 [(3.61±2.17) and (0.94±0.25), P<0.05] in the liver tissue of mice in the hyperbaric oxygen group were decreased. The tumor necrosis factor-α protein level [(7.50±4.73) and (1.05±0.58), P<0.05] and interleukin-1β [(1.65±0.35) and (1.02±0.02), P<0.05] was reduced following hyperbaric oxygen treatment compared with those in the model group. Conclusion: Hyperbaric oxygen therapy can slow down the progression of nonalcoholic fatty liver disease by regulating the levels of oxidative stress and inflammation in the mice.
目的： 探讨高压氧治疗对小鼠非酒精性脂肪性肝病的疗效及其机制。 方法： 将21只8周龄雄性C57BL/6J小鼠分为3组，分别为对照组（正常饮食）、模型组（高脂高胆固醇饮食）、高压氧组（高脂高胆固醇饮食+高压氧治疗），每组小鼠各7只。治疗结束后比较3组小鼠体质量、血清转氨酶和血脂的变化，通过苏木精-伊红染色、油红O染色、天狼星红染色以及F4/80免疫组织化学染色观察肝脏组织病理学改变，通过RT-qPCR和蛋白质印迹方法检测氧化应激及炎性因子的表达水平。各组间的比较采用单因素方差分析。 结果： 高压氧组小鼠肝脏组织病理学明显改善，血清学丙氨酸转氨酶、天冬氨酸转氨酶及胆固醇水平分别为（77.50±13.59）U/L、（156.06±23.68）U/L和（4.80±0.53）mmol/L，显著低于模型组［（109.43±16.88）U/L、（216.62±18.79）U/L和（5.86±0.53）mmol/L，P<0.05］，同时伴有较低的脂质沉积、巨噬细胞浸润和纤维化水平；此外，经高压氧治疗后，肝脏组织抗氧化应激蛋白核转录因子红系2相关因子2［（0.30±0.06）和（2.16±1.21），P<0.05］和血红素加氧酶-1［（0.48±0.19）和（1.01±0.18），P<0.05］的表达较模型组有上升趋势，转录水平上也得到了验证（P<0.05）。同时，相较于模型组，高压氧组小鼠肝组织肿瘤坏死因子-α［（2.60±0.71）和（0.66±0.15），P<0.05］、白细胞介素-1β［（2.41±1.01）和（0.78±0.23），P<0.05］、白细胞介素-6［（3.61±2.17）和（0.94±0.25），P<0.05］的mRNA表达均降低，而在蛋白水平上，予以高压氧处理后的肿瘤坏死因子-α［（7.50±4.73）和（1.05±0.58），P<0.05］、白细胞介素-1β［（1.65±0.35）和（1.02±0.02），P<0.05］的含量也较模型组减少。 结论： 高压氧治疗可以通过调节肝脏氧化应激及炎症水平从而减缓非酒精性脂肪性肝病小鼠的疾病进展。.