摘要：
目的 探讨胸腺素β4在治疗非酒精性脂肪性肝病(NAFLD)中的作用及机制.方法 将40只雄性C57BL/J6小鼠分为正常组、NAFLD组、低剂量胸腺素p4组、高剂量胸腺素β4组,每组10只.采用高脂高糖饮食喂养16周制备NAFLD模型,低剂量、高剂量胸腺素β4组分别腹腔注射胸腺素β40.05 mg·kg-1 ·d-1和0.20mg· kg-1·d1,共8周.检测肝功能相关指标和血清TNF-α水平,光学显微镜下观察肝组织病理学变化并行非酒精性脂肪性肝病活动度评分(NAS),蛋白质印迹法检测肝组织NF-κB p65、核因子κB抑制蛋白α(IκBa)蛋白质表达水平,免疫组织化学法检测肝组织TNF-α表达,计算平均积分吸光度(MIA).组间比较采用t检验.结果 高剂量胸腺素β4组ALT、GGT、血清TNF-α水平均低于NAFLD组[分别为(28±17) U/L比(76±29) U/L,(61±39) U/L比(102±56) U/L,(144.1±48.2) ng/L比(187,3±58.8)ng/L],差异均有统计学意义(t=4.52、2.78、2.30,P均＜0.05).低剂量胸腺素β4组、高剂量胸腺素β4组NAS均低于NAFLD组[分别为(3.7±0.4)、(2.3±0.3)比(4.6±0.3)分],差异均有统计学意义(t=5.69、17.14,P均＜0.01).NAFLD组胸腺素β4相对表达水平低于正常组(0.2±0.1比1.4±0.6),差异有统计学意义(t=6.24,P＜0.01);高剂量胸腺素β4组胸腺素β4和IκBa相对表达水平均高于NAFLD组(分别为1.0±0.3、0.5±0.3比0.2±0.1),差异均有统计学意义(t=8.00、3.00,P均＜0.01);高剂量胸腺素β4组肝组织NF-κB p65相对表达水平低于NAFLD组(0.6±0.3比1.5士0.7),差异有统计学意义(t=3.74,P＜0.01).高剂量胸腺素β4组MIA低于NAFLD组(0.4±0.2比0.7±0.3),差异有统计学意义(t=2.63,P＜0.01).结论 胸腺素β4可有效治疗NAFLD,可能是通过抑制NF-κB通路发挥作用.%Objective To explore the role and mechanism of thymosin β4 (Tβ4) in the treatment of non-alcoholic fatty liver disease (NAFLD).Methods Forty male C57BL/J6 mice were divided into normal group,NAFLD group,low dose Tβ4 group and high dose Tβ4 group with 10 mice in each group.NAFLD mice model was established by feeding with high fat and high sugar diet for 16 weeks.The mice in low-dose Tβ4 group and high dose Tβ4 group were intraperitonealy injected with Tβ4 at 0.05 mg · kg-1 · d-1 and 0.20 mg · kg-1 · d-1,respectively,for eight weeks.The liver function indexes and serum tumor necrosis factor-α (TNF-α) level were detected;the pathological changes of liver tissue were observed under optical microscope and non-alcoholic fatty liver disease activity score (NAS) was evaluated.The protein expression levels of nuclear factor-κB p65 (NF-κB p65) and nuclear factor κB inhibit protein a (IκBa) at the protein level in liver tissue were measured by Western blotting method.The expression of TNF-α in liver tissue was detected by immunohistochemistry.Mean integral absorbance (MIA) was calculated.T test was performed for groups comparison.Results The levels of alanine aminotransferase (ALT),γ-glutamine transferase (GGT) and serum TNF-α levels of high dose Tβ4 group were all lower than those of NAFLD group ((28±17) U/L vs.(76±29) U/L,(61±39) U/L vs.(102±56) U/L,(144.1± 48.2) ng/L vs.(187.3±58.8) ng/L,respectively),and the differences were statistically significant (t=4.52,2.78 and 2.30,all P＜0.05).The NAS of low dose Tβ4 group and high dose Tβ4 group were both lower than that of NAFLD group (3.7±40.4,2.3±0.3 vs.4.6±0.3),and the differences were statistically significant (t=5.69 and 17.14,both P＜0.01).The relative expression level of Tβ4 protein of NAFLD group was lower than that of normal group (0.2±0.1 vs.1.4±0.6),and the difference was statistically significant (t=6.24,P＜0.01).The relative expression levels of Tβ4 and IκBa of high dose Tβ4 group were higher than those of NAFLD group (1.0±0.3,0.5±0.3 vs.0.2±0.1),and the differences were statistically significant (t=8.00 and 3.00,both P＜0.01).The relative expression level of NF-κB p65 in liver tissue of high dose Tβ4 group was lower than that of NAFLD group (0.6±0.3 vs.1.5±0.7),and the difference was statistically significant (t=3.74,P＜0.01).The MIA of high dose Tβ4 group was lower than that of NAFLD group (0.4±0.2 vs.0.7±0.3),and the difference was statistically significant (t=2.63,P＜ 0.01).Conclusion Tβ4 can effectively treat NAFLD probably through inhibiting the NF-κB pathway.
