摘要
目的研究IL-12与IL-17在自身免疫性肝病(AILD)患者血清及肝组织中的表达及意义。方法收集21例自身免疫性肝炎(AIH组)、21例原发性胆汁性肝硬化(PBC组)、9例自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征(AIH-PBC OS组)患者外周血和肝组织,采用ELISA法和免疫组织化学法分别检测患者血清及肝组织中IL-12与IL-17的表达,采用常规自动生化分析仪测定丙氨酸氨基转移酶(ALT)和γ-谷氨酰转肽酶(GGT)水平,并分析血清IL-12、IL-17表达与ALT和GGT水平的相关性。选择10例健康体检者和10例正常肝组织作为对照。结果 AIH组、PBC组及AIH-PBC OS组患者血清中IL-12表达水平均低于对照组(P<0.01),IL-17表达水平均高于对照组(P<0.01)。AIH组和PBC组患者血清IL-12与IL-17表达之间呈负相关(AIH:r=-0.752,P<0.05;PBC:r=-0.436,P<0.05);AIH组和PBC组患者血清IL-17表达与ALT和GGT均呈正相关(AIH:r=0.825,P<0.05;PBC:r=0.571,P<0.05)。各组患者肝组织IL-12主要表达在肝内胆管上皮细胞及枯否细胞胞质中,各组阳性表达率均低于对照组[AIH:19.05%(4/21),PBC:9.52%(2/21),AIHPBCOS:11.11%(1/9),对照:90.00%(9/10);P<0.01];IL-17主要表达在淋巴细胞和单核细胞胞质中,各组阳性表达率均高于对照组[AIH:71.43%(15/21),PBC:76.19%(16/21),AIH-PBC OS:77.78%(7/9),对照:10.00%(1/10);P<0.01];AIH组和PBC组患者肝组织IL-12与IL-17表达之间呈负相关(AIH:r=-0.499,P=0.021;PBC:r=-0.580,P=0.006)。结论在AILD中,IL-12表达降低,对Th17细胞分化的抑制作用减弱,进而产生过多的IL-17,介导了炎症损伤,IL-12/IL-17炎症通路可能参与了AILD的发生发展。
Objective To investigate the expression of interleukin （IL）-12 and IL-17 in the serum and liver tissues of patients with autoimmune liver disease （AILD） and to discuss the relevant significance. Methods The peripheral blood and liver tissues were collected from 21 patients with autoimmune hepatitis （AIH）, 21 with primary biliary cirrhosis （PBC）, and 9 with AIH-PBC overlap syndrome （AIH PBC OS）. The serum IL-12 and IL-17 levels were assayed by ELISA, and the expression and location of IL-12 and IL-17 in the liver tissues were detected by immunohistochemistry method. Alamine transaminase（ALT） and r-glutamyltransferase（GGT） were measured by automatic biochemical analyzer. The correlation of serum IL-12 and IL-17 expressions with ALT and GGT levels was analyzed. Ten healthy participants taking a physical examination and 10 normal liver tissues were used as controls. Results The serum levels of IL-12 in AIH, PBC, and AIH-PBC OS groups were significantly lower than that in the control group（P〈0.01）, and the serum levels of IL-17 in the three groups were significantly higher than that in the control group（P〈0.01）. A negative correlation was found between serum IL-12 and IL-17 in AIH and PBC groups （AIH： r=-0. 752,P〈0.05;PBC：r=-0. 436, P〈0.05）, and serum IL-17 was positively correlated with ALT and GGT （AIH： r=0. 825, P〈0.05;PBC：r=0. 571, P〈0.05）. IL-12 was mainly expressed in bile duct epithelium and Kupffer cells, and the expression rates in the 3 experimental groups were significantly lower than that in the control group （AIH： 19.05%0 [4/21], PBC： 9.52%[2/21], AIH-PBC OS： 11.11% [1/9], control： 90.00% [9/10]; P〈 0.01）. IL-17 was mainly expressed in lymphocytes and monoeytes, and the expression rates in the 3 experimental groups were significantly higher than that in control group （AIH： 71.43%[15/21], PBC： 76.19%[16/21], AIH-PBC OS： 77.78%[7/ 9], control： 10.00% [1/10]; P〈0.01）. IL 12 expression in the liver tissues was negatively correlated with IL-17 expression inAIH and PBCgroups（AIH：r=-0. 499, P=0. 021; PBC： r=-0. 580,P= 0. 006）. Conclusion IL-12 expression is reduced in AILD patients, decreasing the inhibition against Thl7 cell differentiation, leading to IL-17 increase and mediating inflammatory injury, which indicates that IL 12/IL-17 inflammatory pathway may participate in the development and progression of AILD.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2013年第5期531-535,共5页
Academic Journal of Second Military Medical University
