【摘要】 目的 观察外周血辅助性T淋巴细胞9(helper T cell 9,Th9)、辅助性T淋巴细胞22(helper T cell 22,Th22)及其效应因子在药物性肝损伤(drug-induced liver injury, DILI)中的表达及意义。方法 选择56例DILI患者为DILI组，15例健康志愿者为健康对照组，其中DILI组分为轻度肝损伤组(n=15)、中度肝损伤组(n=15)、重度肝损伤组(n=15)、急性肝衰竭组(n=11)4组，治疗前后分别检测血清肝功能、外周血Th9、Th22,血清白细胞介素-9(interleukin-9,IL-9)、白细胞介素-22(interleukin-22,IL-22)等指标，观察并分析Th9、Th22、IL-9、IL-22在DILI中的变化，以及其与肝损伤程度及类型的关系。结果 轻度肝损伤组治疗前后总胆红素(total bilirubin, TBIL)、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotranferase, AST)、碱性磷酸酶(alkaline phosphatase, ALP)差异均有统计学意义(t分别为5.777、10.347、4.225、2.948,P均<0.05),国际标准化比值(international normalized ratio, INR)差异无统计学意义(t=0.210,P>0.05);中度肝损伤组治疗前后TBIL、ALT、AST、ALP、INR差异均有统计学意义(t分别为7.642、5.842、5.747、3.924、5.206,P均<0.05);重度肝损伤组治疗前后TBIL、ALT、AST、ALP、INR差异均有统计学意义(t分别为6.410、5.369、4.726、3.893、6.487,P均<0.05);急性肝衰竭组治疗前后TBIL、ALP、INR差异无统计学意义(t分别为0.669、0.072、0.521,P均>0.05),ALT、AST差异有统计学意义(t分别为5.466、7.184,P均<0.05)。DILI组外周血Th9、Th22及相关细胞因子血清IL-9、IL-22均较健康对照组升高，两组比较差异均有统计学意义(t分别为2.269、2.481、6.014、4.987,P均<0.05)。轻度肝损伤组、中度肝损伤组治疗前后Th9、Th22、IL-9、IL-22差异均有统计学意义(t分别为3.556、-5.906、8.258、-2.219、5.906、-8.500、7.982、-5.403,P均<0.05);重度肝损伤组治疗前后Th9、IL-9差异有统计学意义(t分别为8.411、7.250,P均<0.05),Th22、IL-22差异无统计学意义(t分别为-1.463、-2.038,P均>0.05);急性肝衰竭组治疗前后Th9、IL-9差异无统计学意义(t分别为1.614、0.504,P均>0.05),Th22、IL-22差异有统计学意义(t分别为-3.825、-2.482,P均<0.05)。不同类型肝损伤外周血Th9、Th22及IL-9、IL-22差异均无统计学意义(F分别为0.636、0.330、0.051、0.376,P均>0.05)。Th9与ALT呈正相关(r=0.547,P<0.001);Th22与TBIL呈负相关(r=-0.657,P<0.001),与ALT呈负相关(r=-0.301,P=0.024)。结论 外周血Th9、Th22及相关细胞因子IL-9、IL-22参与了DILI发病机制，Th9可能起促炎作用，Th22可能起抗炎作用，其与肝损伤类型可能无关。更多还原

【Abstract】 Objective To observe the expression and significance of helper T cells 9(Th9), helper T cells 22(Th22) and their effector factors in peripheral blood of drug-induced liver injury(DILI). Methods Fifty-six patients with DILI were selected as DILI group and 15healthy volunteers as healthy control group. The DILI group was divided into four groups: mild liver injury group(15 cases), moderate liver injury group(15 cases), severe liver injury group(15 cases) and acute liver failure group(11 cases). Meanwhile, serum liver function, peripheral blood Th9 and Th22, serum interleukin-9(IL-9) and interleukin-22(IL-22) were detected before and after treatment. To observe and analyze the changes of Th9, Th22, IL-9 and IL-22 in DILI, as well as their relationship with the degree and type of liver injury. Results There were significant differences in total bilirubin(TBIL), alanine aminotransferase(ALT), aspartate aminotranferase(AST) and alkaline phosphatase(ALP) before and after treatment in the mild DILI group(t were 5.777, 10.347, 4.225, 2.948; P<0.05), but no significant differences in international normalized ratio(INR)(t=0.210, P>0.05). There were significant differences in TBIL, ALT, AST, ALP and INR before and after treatment in moderate liver injury group(t were 7.642, 5.842, 5.747, 3.924, 5.206; P<0.05). There were significant differences in TBIL, ALT, AST, ALP and INR before and after treatment in severe liver injury group(t were 6.410, 5.369, 4.726, 3.893, 6.487; P<0.05). There were no significant differences in TBIL, ALP and INR before and after treatment in acute liver failure group(t were 0.669, 0.072, 0.521; P>0.05), while there were significant differences in ALT and AST(t were 5.466, 7.184; P<0.05). The levels of Th9 and Th22 in peripheral blood and serum IL-9 and IL-22 of related cytokines in patients with DILI were higher than those in healthy control group, and the differences between the two groups were statistically significant(t were 2.269, 2.481, 6.014, 4.987; P<0.05). There were statistically significant differences in Th9, Th22, IL-9 and IL-22 before and after treatment in mild and moderate liver injury groups(t were 3.556,-5.906, 8.258,-2.219, 5.906,-8.500, 7.982,-5.403; P<0.05). There were statistically significant differences in Th9 and IL-9 before and after treatment in the severe liver injury group(t were 8.411, 7.250; P<0.05), but no significant differences in Th22 and IL-22(t were-1.463,-2.038; P>0.05). There was no significant difference in Th9 and IL-9 before and after treatment in acute liver failure group(t were 1.614, 0.504; P>0.05), but there was significant difference in Th22 and IL-22 before and after treatment(t were-3.825,-2.482; P<0.05). There were no significant differences in Th9, Th22, IL-9 and IL-22 among different types of liver injury(F were 0.636, 0.330, 0.051, 0.376; P>0.05). Th9 was positively correlated with ALT(r=0.547, P<0.001). Th22 was negatively correlated with TBIL(r=-0.657, P<0.001) and ALT(r=-0.301, P=0.024). Conclusion Peripheral blood Th9, Th22 and related cytokines IL-9 and IL-22 are involved in the pathogenesis of DILI. Th9may play a pro-inflammatory role, while Th22may play an anti-inflammatory role, which may have nothing to do with the type of liver injury.更多还原