浙江大学学报（医学版）
浙江大學學報（醫學版）
절강대학학보（의학판）
JOURNAL OF ZHEJIANG UNIVERSITY MEDICAL SCIENCES
2015年
2期
154-161
,共8页
翁跃颂%王华英%吕定丰%傅中明%俞万钧
翁躍頌%王華英%呂定豐%傅中明%俞萬鈞
옹약송%왕화영%려정봉%부중명%유만균
结节病%T淋巴细胞%T淋巴细胞,辅助诱导%糖皮质激素类
結節病%T淋巴細胞%T淋巴細胞,輔助誘導%糖皮質激素類
결절병%T림파세포%T림파세포,보조유도%당피질격소류
Sarcoidosis%T-lymphocytes%T-lymphocytes,helper-inducer%Glucocorticoids
目的：观察结节病患者辅助性 T 细胞17（ Th17）和调节性 T 细胞（ Treg）的变化及与疾病活动的关系。方法：选择2009年1月～2013年12月在鄞州人民医院治疗的23例结节病患者作为研究对象，以25例健康志愿者作为正常对照组，在糖皮质激素治疗前后分别用酶反应连续监测法测定血清血管紧张素转化酶（SACE），流式细胞术测定外周血和支气管肺泡灌洗液（BALF）中Th17细胞和Treg细胞比例，酶联免疫吸附试验法测定血清及BALF上清液中相关细胞因子水平，实时荧光定量PCR测定外周血转录因子ROR-γt和Foxp3 mRNA表达水平，分析Th17／Treg比值与病情活动的相关性。结果：结节病患者活动期外周血Th17细胞比例较正常对照组明显升高（4.34％±0.89％ vs 1.60％±0.42％），而Treg细胞比例明显降低（1.28％±0.37％ vs 3.39％±0.50％）；转录因子 ROR-γt mRNA表达水平较正常对照组明显升高（21.31±3.55 vs 3.63±1.00），而Foxp3 mRNA明显降低（1.60±0.24 vs 3.12±0.76），差异均有统计学意义（均 P ＜0.01）。糖皮质激素治疗后上述指标均显著改善（外周血Th17细胞比例2.16％±0.68％，Treg细胞比例2.21％±0.42％，转录因子ROR-γt mRNA 水平10.15±1.93，Foxp3 mRNA水平2.44±0.38），差异均有统计学意义（均P＜0.05）。外周血Th17和Treg细胞相关细胞因子的变化与两类细胞比例变化一致；激素治疗后BALF中上述指标变化趋势与外周血一致。 Th17／Treg细胞比值与外周血SACE水平呈显著正相关（ r＝0.781， P＜0.01）。结论：Th17／Treg细胞平衡失调与结节病的活动密切相关，可能参与了结节病的发病过程。
目的：觀察結節病患者輔助性 T 細胞17（ Th17）和調節性 T 細胞（ Treg）的變化及與疾病活動的關繫。方法：選擇2009年1月～2013年12月在鄞州人民醫院治療的23例結節病患者作為研究對象，以25例健康誌願者作為正常對照組，在糖皮質激素治療前後分彆用酶反應連續鑑測法測定血清血管緊張素轉化酶（SACE），流式細胞術測定外週血和支氣管肺泡灌洗液（BALF）中Th17細胞和Treg細胞比例，酶聯免疫吸附試驗法測定血清及BALF上清液中相關細胞因子水平，實時熒光定量PCR測定外週血轉錄因子ROR-γt和Foxp3 mRNA錶達水平，分析Th17／Treg比值與病情活動的相關性。結果：結節病患者活動期外週血Th17細胞比例較正常對照組明顯升高（4.34％±0.89％ vs 1.60％±0.42％），而Treg細胞比例明顯降低（1.28％±0.37％ vs 3.39％±0.50％）；轉錄因子 ROR-γt mRNA錶達水平較正常對照組明顯升高（21.31±3.55 vs 3.63±1.00），而Foxp3 mRNA明顯降低（1.60±0.24 vs 3.12±0.76），差異均有統計學意義（均 P ＜0.01）。糖皮質激素治療後上述指標均顯著改善（外週血Th17細胞比例2.16％±0.68％，Treg細胞比例2.21％±0.42％，轉錄因子ROR-γt mRNA 水平10.15±1.93，Foxp3 mRNA水平2.44±0.38），差異均有統計學意義（均P＜0.05）。外週血Th17和Treg細胞相關細胞因子的變化與兩類細胞比例變化一緻；激素治療後BALF中上述指標變化趨勢與外週血一緻。 Th17／Treg細胞比值與外週血SACE水平呈顯著正相關（ r＝0.781， P＜0.01）。結論：Th17／Treg細胞平衡失調與結節病的活動密切相關，可能參與瞭結節病的髮病過程。
목적：관찰결절병환자보조성 T 세포17（ Th17）화조절성 T 세포（ Treg）적변화급여질병활동적관계。방법：선택2009년1월～2013년12월재은주인민의원치료적23례결절병환자작위연구대상，이25례건강지원자작위정상대조조，재당피질격소치료전후분별용매반응련속감측법측정혈청혈관긴장소전화매（SACE），류식세포술측정외주혈화지기관폐포관세액（BALF）중Th17세포화Treg세포비례，매련면역흡부시험법측정혈청급BALF상청액중상관세포인자수평，실시형광정량PCR측정외주혈전록인자ROR-γt화Foxp3 mRNA표체수평，분석Th17／Treg비치여병정활동적상관성。결과：결절병환자활동기외주혈Th17세포비례교정상대조조명현승고（4.34％±0.89％ vs 1.60％±0.42％），이Treg세포비례명현강저（1.28％±0.37％ vs 3.39％±0.50％）；전록인자 ROR-γt mRNA표체수평교정상대조조명현승고（21.31±3.55 vs 3.63±1.00），이Foxp3 mRNA명현강저（1.60±0.24 vs 3.12±0.76），차이균유통계학의의（균 P ＜0.01）。당피질격소치료후상술지표균현저개선（외주혈Th17세포비례2.16％±0.68％，Treg세포비례2.21％±0.42％，전록인자ROR-γt mRNA 수평10.15±1.93，Foxp3 mRNA수평2.44±0.38），차이균유통계학의의（균P＜0.05）。외주혈Th17화Treg세포상관세포인자적변화여량류세포비례변화일치；격소치료후BALF중상술지표변화추세여외주혈일치。 Th17／Treg세포비치여외주혈SACE수평정현저정상관（ r＝0.781， P＜0.01）。결론：Th17／Treg세포평형실조여결절병적활동밀절상관，가능삼여료결절병적발병과정。
Objective:To investigate the Th17 cell and Treg cell levels in patients with sarcoidosis , and their relation to disease activation and glucocorticoids treatment . Methods:Twenty-three sarcoidosis patients admitted in Yinzhou People's Hospital from January 2009 to December 2013 and 25 healthy subjects ( controls ) were included in this study .The blood samples and bronchoalveolar lavage fluid ( BALF) samples were collected in all patients before and after glucocorticoids treatment . The serum angiotensin converting enzyme (SACE) levels were detected.The percentages of Th17 cells and Treg cells in peripheral blood and BALF were determined by flow cytometry , the concentrations of cytokines in serum and supernatants of BALF were measured by enzyme-linked immunosorbent assay (ELISA).The levels of ROR-γt and Foxp3 mRNA transcripts in peripheral blood mononuclear cells ( PBMC) were determined by real-time quantitative PCR .The potential correlation between the percentages of Th 17 or Treg cells and SACE levels was evaluated . Results: Compared with healthy controls , significantly higher frequencies of Th17 cells (4.34%±0.89%vs 1.60%±0.42%), lower frequencies of Treg cells (1.28%±0.37% vs 3.39%±0.50%) in peripheral blood were observed.Higher level of ROR-γt mRNA (21.31 ±3.55 vs 3.63 ±1.00) and lower level of Foxp3 mRNA (1.60 ±0.24 vs 3.12 ±0.76) in peripheral blood were detected in sarcoidosis patients in active stage ( before glucocorticoids treatment ) ( all P<0 .01 ) .After the treatment of glucocorticoids , these index in peripheral blood were significantly improved (Th17 cells 2.16%±0.68%,Treg cells 2.21%±0.42%, ROR-γt mRNA 10.15 ±1.93, Foxp3 mRNA 2.44 ±0.38) ( all P <0.05).The changing trends of Th 17 and Treg cell cytokines levels in serum were consistent with two type cells.Meanwhile, the changing trends of above index in BALF of patients treated by glucocorticoids were consistent with those in sarcoidosis patients in active stage .The increased ratios of Th17 cells to Treg cells were positively correlated with the level of serum SACE (r=0.781).Conclusion:The imbalance of Th17 cells and Treg cells in peripheral blood and airway may be involved in the pathogenesis of sarcoidosis , which was associated with the activity of disease , and the treatment of glucocorticoids may achieve a therapeutic effect by correcting the immune imbalance .
