a Abadan School of Medical Sciences , Abadan , Iran.
b Department of Pharmacology, Faculty of Pharmacy , Ahvaz Jundishapur University of Medical Sciences (AJUMS) , Ahvaz , Iran.
Immunopharmacol Immunotoxicol. 2018 Jun;40(3):225-231. doi: 10.1080/08923973.2018.1431924. Epub 2018 Feb 15.
Pulmonary fibrosis (PF) is a chronic respiratory system disease. The role of inflammation and angiotensin in the development and progression of PF has previously been demonstrated. Alternation in antifibrotic/profibrotic mediators and NF-κB activation have important roles in PF development. NF-κB, a nuclear factor, induces the transcription of inflammatory and pro-inflammatory cytokines. The aim of this study was to evaluate the effect of valsartan as an angiotensin receptor blocker on IL-4, INF-γ, and NF-κB expression in the treatment of PF.
Rats were divided into five groups: groups I (bleomycin) and II (control) received a single injection of bleomycin (7.5 IU/kg) or vehicle, respectively. Groups III-V received valsartan (20, 40, and 80 mg/kg, respectively) orally a week before and for 3 weeks after the bleomycin injection. Serum levels of IL-4 and INF- γ were then measured. Relative NF-κB expression was investigated by real-time PCR.
Histopathological examination showed the anti-inflammation effect of valsartan. Bleomycin significantly increased IL-4 serum level and decreased that of INF-γ in the serum. Valsartan could restore their levels to normal. Valsartan raised the decreased ratio of INF-γ/IL-4. Exposure to bleomycin elevated NF-κB expression; and valsartan decreased the increased gene expression.
Valsartan as an angiotensin receptor antagonist presumably by blocking angiotensin receptor causes to ameliorated PF, which was at least partly due to antifibrotic/profibrotic cytokine regulation and reduced NF-κB expression.
Valsartan showed a significant protective effect against bleomycin-induced PF.
肺纤维化（PF）是一种慢性呼吸系统疾病。先前已经证明，炎症和血管紧张素在 PF 的发生和发展中起作用。抗纤维化/促纤维化介质的改变和 NF-κB 的激活在 PF 的发展中起重要作用。NF-κB 是一种核因子，可诱导炎症和促炎细胞因子的转录。本研究旨在评估血管紧张素受体阻滞剂缬沙坦对 PF 治疗中 IL-4、INF-γ 和 NF-κB 表达的影响。
大鼠分为五组：I 组（博来霉素）和 II 组（对照组）分别单次注射博来霉素（7.5IU/kg）或赋形剂。III-V 组分别口服缬沙坦（20、40 和 80mg/kg），在博来霉素注射前一周和后三周。然后测量血清中 IL-4 和 INF-γ 的水平。通过实时 PCR 研究相对 NF-κB 表达。
组织病理学检查显示缬沙坦具有抗炎作用。博来霉素显著增加了血清中 IL-4 的水平并降低了血清中 INF-γ 的水平。缬沙坦可将其水平恢复正常。缬沙坦提高了降低的 INF-γ/IL-4 比值。暴露于博来霉素会增加 NF-κB 的表达；缬沙坦可降低基因表达的增加。
血管紧张素受体拮抗剂缬沙坦可能通过阻断血管紧张素受体导致 PF 得到改善，这至少部分是由于抗纤维化/促纤维化细胞因子的调节和 NF-κB 表达的降低。
缬沙坦对博来霉素诱导的 PF 具有显著的保护作用。
