Th17细胞在肺纤维化大鼠模型中的表达

Expressions of Th17 cell in rat model of pulmonary fibrosis

摘要:

目的：初步探讨肺纤维化（pulmonary fibrosis，PF）大鼠模型肺组织中Th17细胞转表达的机制。方法：54只雄SD大鼠采用随机数字表法分为生理盐水对照组（N组）、ＰＦ模型组（B组）、地塞米松治疗组（D组），每组18只。B、D组采用气管内注入博来霉素（5 mg/kg）构建大鼠PF模型，N组气管内注射生理盐水作为对照；D组在PF模型基础上第2天开始每日腹腔注射地塞米松注射液3 mg/kg；N、B组腹腔注射生理盐水注射液。各组大鼠分别于第7、14、28天处死。HE评价各组各时间点肺组织病理形态学变化并测肺组织匀浆中羟脯氨酸（hydroxyproline，HYP）含量；流式细胞仪检肺组织CD4+IL-17+Th17细胞；ELISA测血清白介素-17（interleukin-17，IL-17） 水平。结果：① B组肺组织病理变化表现为由肺泡炎至纤维化的动态改变过程，肺组织内HYP均高于D组和N组（P<0.05），第28 天时数值最高；②Th17细胞在N组呈低水平表达；B、D组在不同时间点与N组比较肺组织中Th17细胞和血清中IL-17表达均明显增高（P<0.05），以造模第7天最为显著。结论：PF是由炎症性损伤及其修复而动态发展形成的，不同时间点有着不同的病理变化特征。PF大鼠模型肺组织Th17细胞和血清IL-17 表达增高，与肺部炎症、PF密切相关，参与PF形成过程。

Abstract:

Objective：To investigate expressions of Th17 cell in rat model of pulmonary fibrosis（PF）. Methods：Totally 54 SD rats were randomly divided into 3 groups：control group（N group，n=18），PF model group（B group，n=18） and dexmethasone treated group（D group）. B and D groups were established by a single intra-tracheal injection of 5 mg/kg of bleomycin. N group received intra-tracheal instillation of saline instead. The next day D group was injected with dexamethasone（3 mg/kg） intraperitoneally every other day while N and B groups were injected with saline. Rats were sacrificed at the 7th，14 th，28th d after modeling in batch. Lung tissues were re－stored to analyze the pathological changes with HE staining and levels of hydroxyproline（HYP） in pulmonary tissues were determined. Proportion of CD4+IL-17+Th17 cells in the lung was evaluated by flow cytometry. Levels of serum interleukin-17（IL-17） were mea－sured by ELISA. Results：①In B group，biopsy of pulmonary tissues showed the dynamic process of change from pulmonary alveolitis to PF gradually. Levels of HYP in pulmonary tissues were higher in B group（the highest on the 28th d） than in N and D groups（P<0.05）. ②Th17 cell was lowly expressed in N group. Expressions of Th17 cell in pulmonary tissues and serum IL-17 were significant－ly higher in B and D groups than in N group at all time points（P<0.05），being most obviously at the 7th d. Conclusions：PF is developed by inflammatory damage and repair and has different pathological characteristics at different time points. Increased expres－sions of Th17 cell in pulmonary tissues of PF rats and serum IL-17 are associated with pulmonary inflammation and PF.