非酒精性脂肪性肝病患者病情进展与T细胞水平的相关性研究

Correlation between disease progression and levels of T cells in patients with non-alcoholic fatty liver disease

  • 摘要: 目的 探讨非酒精性脂肪性肝病(NAFLD)患者病情进展与辅助性T 细胞17(Th17)、调节性T细胞(Treg)水平的相关性。 方法 选取非酒精性脂肪性肝炎(NASH)患者、非酒精性脂肪肝(NAFL)患者以及健康对照者各25例,比较3组肝脏病变程度相关指标[丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、总胆红素(TBil)、直接胆红素(DBil)]、肝纤维化4项[Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)、层黏连蛋白(LN)、透明质酸酶(HA)], 分析外周血Th17、Treg及相关炎症因子[白细胞介素-10(IL-10)、白细胞介素-17(IL-17)]与肝脏病变程度相关性。 结果 3组患者年龄、性别分布、吸烟史、高血压病、肝硬化家族史比较差异无统计学意义(P>0.05); 对照组合并糖尿病者7例,显著少于NAFL组18例和NASH组19例(P<0.05)。3组外周血Th17、Treg、IL-10、IL-17水平两两比较,差异均有统计学意义(P<0.05)。NASH组ALT、AST水平显著高于其他2组(P<0.05); NAFL组ALT水平显著低于对照组(P<0.05), AST水平显著高于对照组(P<0.05)。NASH组TBil、DBil水平与NAFL组、对照组比较均差异有统计学意义(P<0.05)。NASH组PCⅢ、Ⅳ-C、LN、HA水平以及Fibro-touch评分均显著高于其他2组(P<0.05), 且NAFL组HA水平显著高于对照组(P<0.05)。相关性分析结果显示, Th17、IL-17与ALT、AST、TBil、DBil、PCⅢ、Ⅳ-C、LN、HA、Fibro-touch评分、病情程度呈显著正相关(P<0.001), Treg、IL-10与ALT、AST、TBil、DBil、PCⅢ、Ⅳ-C、LN、HA、Fibro-touch评分、病情程度呈显著负相关(P<0.001)。 结论 NAFLD患者外周血中Th17/Treg比例失衡, Th17、Treg表达水平与病情严重程度高度相关,可作为评估NAFLD病情进展的有效指标。

     

    Abstract: Objective To explore the correlation between the disease progression and the levels of T helper type 17(Th17)cells, regulatory T(Treg )cells in patients with non-alcoholic fatty liver disease(NAFLD). Methods A total of 25 patients with non-alcoholic fatty liver(NAFL), 25 cases with non-alcoholic fatty hepatitis(NAFSH)and 25 healthy controls were selected, The indexes related to liver lesions in the three groups [alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBil), direct bilirubin(DBil)], and four indicators of liver fibrosis [procollagen Ⅲ(PCⅢ), type Ⅳ collagen(Ⅳ-C), laminin(LN), and hyaluronidase(HA)] of the three groups were compared, and correlations between Th17, Treg cells as well as related inflammatory factors[Interleukin-10(IL-10), interleukin-17(IL-17)] and degree of liver fibrosis were analyzed. Results There were no significant differences in age, sex distribution, smoking history, hypertension and family history of cirrhosis among the three groups(P>0.05). The number of patients with diabetes in the control group was seven cases, which was significantly lower than 18 cases in the NAFL group and 19 in the NASH group(P<0.05). The levels of Th17, Treg, IL-10 and IL-17 in peripheral blood showed significant between-group differences(P<0.05). The levels of ALT and AST in the NASH group were significantly higher than those in the other two groups(P<0.05). ALT level in the - NAFL group was significantly lower(P<0.05), and AST level in the NAFL group was significantly higher than that in the control group(P<0.05). The levels of TBil and DBil in the NASH group showed significant differences compared to the NAFL group and the control group(P<0.05). The levels of PCⅢ, Ⅳ-C, LN, HA and fibro-touch score in the NASH group were significantly higher than those in the other two groups(P<0.05), and HA level in the NAFL group was significantly higher than that in the control group(P<0.05). The results of correlation analysis showed that ALT, AST, TBil, DBil, PCⅢ, Ⅳ-C, LN, HA, fibro-touch score, and degree of disease had significant positive correlation with Th17 as well as IL-17(P<0.001), and significant negative correlation with IL-10 and Treg(P<0.001). Conclusion The patients with NAFLD showed a unbalanced ratio of Th17/Treg in peripheral blood. Their expression levels are highly correlated with the severity of the disease, and can be effective indicators for monitoring the progression of NAFLD.

     

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