非诺贝特对酒精性肝病患者肝脏巨噬细胞极化及肝纤维化指标的影响

Effects of fenofibrate on liver macrophage polarization and liver fibrosis indexes in patients with alcoholic liver disease

目的探究非诺贝特对酒精性肝病患者肝脏巨噬细胞极化及肝纤维化指标的影响。方法选择2018年1月至2022年9月丽水市第二人民医院住院治疗的100例酒精性肝病患者作为研究对象,采用奇偶数字法将患者随机分为研究组和对照组,每组各50例。对照组入组后进行常规干预治疗,研究组在对照组的基础上口服非诺贝特片,连续治疗2个月。采用流式细胞术检测肝脏巨噬细胞的表型。采用蛋白质印迹法测定肝组织中M1型和M2型巨噬细胞标志物水平。比较2组的临床疗效,以及肝功能、肝纤维化和血脂指标的水平。结果研究组治疗后的总有效率为88.00%,显著高于对照组(72.00%),差异有统计学意义(P<0.05)。经治疗后,研究组肝脏巨噬细胞中M1促炎型巨噬细胞(CD45^(+)F4/80^(+)CD11B^(﹣)CD86^(+))的占比显著低于对照组,M2抑炎型巨噬细胞(CD45^(+)F4/80^(+)CD11B^(﹣)CD206^(+))的占比显著高于对照组,差异均有统计学意义(P均<0.05)。治疗后,研究组肝组织中诱导型一氧化氮合酶(iNOS)、IL-1β水平均显著低于对照组,而IL-10、精氨酸酶-1(Arg-1)水平均显著高于对照组,差异均有统计学意义(P均<0.05)。治疗后,研究组血清ALT、AST、总胆红素(TBil)、γ-谷氨酰转移酶(GGT)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)、总胆固醇(TC)和三酰甘油(TG)水平均显著低于对照组,差异均有统计学意义(P均<0.05)。结论非诺贝特能有效降低酒精性肝病患者的血脂水平,抑制肝纤维化进展,改善肝功能,其作用机制可能与调节肝脏巨噬细胞极化有关。

Objective This paper aims to investigate the effect of fenofibrate on liver macrophage polarization and liver fibrosis indexes in patients with alcoholic liver disease.Methods A total of 100 patients with alcoholic liver disease hospitalized in the Second People's Hospital of Lishui from January 2018 to September 2022 were selected and randomly assigned into the study group and the control group with 50 cases in each group by using the odd-even number method.The control group was given routine intervention treatment after entering the group,while the study group was given fenofibrate tablets on the basis of the routine intervention treatment of the control group for 2 months.The phenotype of hepatic macrophages was detected by flow cytometry while the levels of M1 and M2 macrophage markers in liver tissue were determined by Western blotting.The clinical efficacy,liver function,liver fibrosis and blood lipid indexes of the two groups were compared.Results The total effective rate of the study group is 88.00%,which is higher than that of the control group(72.00%),with statistically significant differences(P<0.05).After treatment,the proportion of M1 pro-inflammatory macrophages(CD45^(+)F4/80^(+)CD11B^(﹣)CD86^(+))in the study group is lower than that in the control group,while the proportion of M2 antiinflammatory macrophages(CD45^(+)F4/80^(+)CD11B^(﹣)CD206^(+))is higher than that in the control group,with statistically significant differences(P<0.05).After treatment,the levels of inducible nitric oxide synthase(iNOS)and interleukin-1β(IL-1β)in the liver tissue of the study group are lower than those of the control group,while the levels of interleukin-10(IL-10)and arginase-1(Arg-1)in the study group are higher than those of the control group,with statistically significant differences(P<0.05).After treatment,the serum levels of ALT,AST,total bilirubin(TBil),gamma gluta transferase(GGT),hyaluronic acid(HA),laminin(LN),typeⅢprocollagen(PCⅢ),typeⅣcollagen(Ⅳ-C),total cholesterol(TC),and triglyceride(TG)are lower than those in the control group,with statistically significant differences(P<0.05).Conclusion Fenofibrate can effectively reduce the level of blood lipids,inhibit the progression of liver fibrosis,and improve liver function in patients with alcoholic liver disease,and its mechanism may be related to the regulation of polarization of hepatic macrophages.