甘草酸二铵、多烯磷脂酰胆碱对抗结核药物所致肝损伤的保护作用比较

Protective effects of diammonium glycyrrhizinate and polyene phosphatidyl choline on livery damage caused by anti-tuberculosis drugs

目的:研究甘草酸二铵、多烯磷脂酰胆碱对抗结核药物所致肝损伤的保护作用。方法:选择在我院接受2HRS(E)Z/4HR短程抗结核治疗的初治肺结核患者,随机分为甘草酸二铵组(A组)和多烯磷脂酰胆碱(B组),保肝治疗4周后检测血清中肝损伤标志分子、应激状态标志分子、NF-κB介导炎症分子的含量以及胆汁酸代谢基因的蛋白表达量。结果:B组血清中ALT、AST、GGT、ALP、GDH、TBIL、NF-κB、IL-1β、TNF-α、MCP-1的含量均显著低于A组(P<0.05),HO-1、GSH-Px、SOD、ERK、MEK、SIRT1的含量均显著高于A组(P<0.05);B组血清中CYP7A1、FXR、SHP的蛋白表达量显著低于A组(P<0.05),BESP的蛋白表达量显著高于A组(P<0.05)。结论:多烯磷脂酰胆碱对抗结核药物所致肝损伤的保护作用优于甘草酸二铵,增强HO-1和SIRT1所介导的抗氧化作用、抑制NF-κB介导的炎症反应、调节胆汁酸代谢基因的表达是多烯磷脂酰胆碱发挥保肝作用的分子机制。

Objective：To study the protective effects of diammonium glycyrrhizinate and polyene phosphatidyl choline on livery damage caused by anti-tuberculosis drugs.Methods：Patients who received initial 2HRS（E）Z/4HR short-range antituberculosis treatment in our hospital were selected and randomly divided into diammonium glycyrrhizinate group（group A）and polyene phosphatidyl choline group（group B）,and after 4weeks of liver protection treatment,serum levels of liver damage marker molecules,stress marker molecules and NF-κB-mediated inflammatory molecules as well as protein expression levels of bile acid metabolism genes were determined.Results：Serum ALT,AST,GGT,ALP,GDH,TBIL,NF-κB,IL-1β,TNF-αand MCP-1levels of group B were significantly lower than those of group A while HO-1,GSH-Px,SOD,ERK,MEK and SIRT1 levels were significantly higher than those of group A;serum CYP7A1,FXR and SHP protein expression levels of group B were significantly lower than those of group A while BESP protein expression level was significantly higher than that of group A.Conclusion：Polyene phosphatidyl choline has better protective effect on liver damage caused by anti-tuberculosis drugs than diammonium glycyrrhizinate,and the molecular mechanisms of polyene phosphatidyl choline to protect the liver areenhancing the antioxidant effect mediated by HO-1and SIRT1,inhibiting the inflammatory response mediated by NF-κB and regulating the expression of bile acid metabolism genes.