Expression Of Interleukin-17、21and Orphan Nuclear Receptor Gamma T In The Smoking Rats And The Therapeutic Effect Of Simvaststin And Its Mechanism

Objective:(1)The present study was conducted to observe theexpression of IL-17、IL-21and RORγt in the lung tissue of the smokingrats.(2)To research the effect of IL-17、IL-21and RORγt on the occurrenceand development of COPD.(3)To study the effect and mechanism ofsimvaststin in COPD.Methods:1Preparation of COPD model:36SD rats were randomly divided intoControl group,Smoking group or Treatment group. Smoking group andTreatment group were treated with cigarette-smoke inhalation for16weeks.Meanwhile,simvaststin,at a dose of5mg/kg,was intragasttric administrationone time a day in the Treatment group for16weeks.(2) At the end of16week,The weight of rats were detected,then total and differential cell counts inBALF were done, meanwhiles the pathomorphological changes, includingmean linear intercept (MLI)，mean alveolar numbers (MAN) in rat lung tissueswere measured with ImageJ system.2IL-17、 IL-21and RORγt expression were assessed usingimmunohistoc-hemistry in peripheral lung tissue. IL-17、 IL-21and RORγtmRNAs expression in rat lung tissue was measured by real-time quantitativePCR.Results:1The development of weight in Smoking group rats and Treatmentgroup rats were significantly inhibited compared with control group(P<0.01),but there were no difference between Smoking group and Treatmentgroup at the end of16week(P>0.05). Compared with Control group rats,Thenumber of neutrophils, macrophagocytes, lymphocytesand and total white blood cells in BALF of rats in smoking group were increased (P<0.01). Themean lining interval (MLI) was highter and the mean alveolar number (MAN)was significantly decreased than Control group(P<0.01). Compared withSmoking group and Treatment group, simvastatin had influence on thenumber of neutrophils, macrophagocytes, total white cells, andMAN(P<0.01or P<0.05), but MLI(P>0.05) had no difference.2The result of Immunohistochemistry showed that in small airway layersthe expression of IL-17+cells: Control group（5.20士4.94）cells／㎜2，Smoking gruop（90.00士14.02）cells／㎜2，Treatment group（72.80士10.79）cells／㎜2；the expression ofIL-21+cells：Control group（8.20士3.16）cells／㎜2，Smoking gruop（61.18士9.16）cells／㎜2，Treatment group（49.40士3.34）cells／㎜2；the expression of：Control group（6.80士5.85）cells／㎜2，Smoking gruop（77.27士7.95）cells／㎜2，Treatment group（65.40士5.23）cells／㎜2; In the Bronchial epithelium of the small airway,The percentage of IL-17immunoreactive cells: Control Group（8.60士4.84）％，Smoking Group（77.09士6.49）％，Treatment Group（68.80士10.09）％；The percentage of IL-21immunoreactive cells：Control Group（6.20士5.07）％，Smoking Group（58.45士6.56）％，Treatment Group（48.90士4.15）％；The percentage of RORγt immunoreactive cells：Control Group（7.60士3.78）％，Smoking Group（79.45士6.80）％，Treatment Group（68.50士10.37）％；The number of IL-17+cells in the small airways layerswas significant positively correlated with the mean linearintercept(MLI)(r=0.729, P<0.01) and had a significant negative correlationwith the mean alveolar number (MAN)（r=﹣0.889，P<0.01）.3The results of QuantitativePCR showed that，the mRNA expressionlevel of lung tissue IL-17in the Control group was (4.78±0.51)，Smokinggroup was (1.96±0.60),Treatment group was (3.56±0.15); RORgamrnat inthe Control group was (4.69±0.82)， Smoking group was(2.68±0.08),Treatment group was (3.89±0.21); IL-21in the Control groupwas (5.51±0.86)，Smoking group was (1.99±0.61),Treatment group was(3.59±0.13);compared with each group,the three groups had significant difference（P<0.05或P<0.01）.Conclusion:1Simvastatin inhibited inflammation reaction and the destroy of lungtissue in cigarette smoke-induced rats.2IL-17and relevant factor played important role in inflammationreaction of pulmonary and the destruction lung tissue.Simvastatinameliorated the development of cigarette smoke-induced emphysema in rats,partly by inhibited IL-17and relevant factor.