白细胞介素-17在系统性硬化病小鼠模型中的表达及与转化生长因子-β1的相关性

目的 研究白细胞介素(IL)-17在系统性硬化病(SSc)小鼠模型中的表达、意义及与转化生长因子(TGF)-β1的相关性.方法 30只雌性BALB/c小鼠按随机数字表法分为3组:对照组、博莱霉素注射4周(模型组1)和模型组1停止注射博莱霉素4周(模型组2).观察小鼠皮肤、肺部的炎症和胶原沉积的情况,荧光定量聚合酶链反应(PCR)法检测小鼠皮肤和肺部维甲酸相关孤核受体(RORγt)、IL-17A、TGF-β1mRNA的表达,酶联免疫吸附法检测血清和支气管肺泡灌洗(BALF)中IL-17、TGF-β1水平,采用方差分析进行统计分析.结果 ①模型组小鼠皮肤和肺部明显炎症细胞浸润,胶原纤维增生,皮肤炎症评分和肺部纤维化评分模型组1(2.5±0.8和3.0±1.8),模型组2(2.4±0.8和3.1±1.2)比对照组(0.9±0.7和0.9±1.0)明显增加,模型组皮肤和肺羟脯氨酸的含量较对照组明显增多(F值分别12.19,8.367,25.11,4.641；P均＜0.05).②与对照组比较,模型组1皮肤和肺部IL-17A mRNA(21±8和20±9)、RORγt mRNA(20±9和19±9)、TGF-β1mRNA(23±6和21±7)的表达量明显增高,模型组1外周血及BALF中IL-17含量明显增高,TGF-β1在BALF中含量增加,但在外周血中的含量明显减少,P均＜0.05.③IL-17A mRNA在皮肤的表达量与皮肤TGF-β1mRNA的表达量、皮肤炎症评分、皮肤羟脯氨酸的含量呈正相关(r值分别为0.514、0.555、0.632,均P＜0.01)；IL-17A mRNA在肺部的表达量与肺部TGF-β1mRNA的表达量、肺部纤维化评分呈正相关(r值分别为0.620和0.437、P＜0.05)；血清IL-17的含量与皮肤和肺羟脯氨酸的含量呈正相关(P＜0.05).结论 IL-17参与SSc全身免疫炎症及局部皮肤、肺部的纤维化病变,可能与TGF-β1有一定的联系,共同作用于SSc皮肤及肺部的纤维化病变.

Expression of interleukin-17 in a murine model of experimental systemic sclerosis and its correlation with transforming growth factor-beta 1

Objective The expression and significance of interleukin (IL)-17 in a murine model of experimental systemic sclerosis (SSc) was studied and its correlation with transforming growth factor-beta 1 (TGF-β1) was explored.Methods Thirty female BALB/c mice were randomly divided into 3 groups,including a control group, bleomycin(BLM) injection for 4 weeks group(model 1 group) and a termination injection of BLM 4 weeks group (model 2 group).The pathological changes of skin and lung were detected.The mRNA expressions of IL-17A,RORγt,TGF-β1 mRNA were evaluated by real-time PCR.Enzyme linked immunosorbent assay was used to measure the levels of IL-17 and TGF-β1 in the serum and bronchoalveolar lavage fluid (BALF).Comparisons among groups were performed by variance analysis.Results Skin and lung of the model groups showed evident inflammatory cell infiltration and increased deposition of collagen fibers.The score of dermal inflammation and lung fibrosis was significantly higher in the model 1 and model 2 groups (2.5±0.8,3.0±1.8), (2.4±0.8,3.1±1.2) as compared to that of the control group (0.9±0.7,0.9±1.0),(F=12.19,8.367,25.11,4.641; all P＜0.05).The amount of hydroxyproline was markedly increased in the model groups than in the control group.Compared with those of the control group,the mRNA levels of IL-17A,RORγt,TGF- 31 in the skin and lung of the model 1 group were higher.The levels of IL-17 in serum and BALF of the model 1 group was significantly increased and the levels of TGF- β1 were increased in BALF and decreased in the serum (all P＜0.05).The mRNA levels of IL-17A in skin and lung had a positive correlation with the mRNA levels of TGF- β1,score of dermal inflammation and lung fibrosis.The levels of IL-17 in serum had a positive correlation with hydroxyproline of the skin and lung.Conclusion IL-17 may participate in systemic immune-mediated inflammation and changes of skin and lung in SSc and when combined with TGF-β1 togetter will cause damage to skin and lung in SSc.