The present study was designed to investigate the anti-rheumatic effects and the mechanism of angiotensin (Ang)-(1–7) in rat models with collagen-induced arthritis (CIA). The CIA model was established using male Wistar rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of the tail. The levels of angiotensin converting enzyme 2 (ACE2)/Ang-(1–7)/Mas receptor (MasR) were reduced in CIA rats. The attenuation of paw swelling and arthritis scores and improvement of indexes of spleen and thymus were done by Ang-(1–7) injection in CIA rats. The increased levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the serum and hind paw were blocked by Ang-(1–7) administration. In addition, enhanced NADPH oxidase (Nox) activity, increased levels of superoxide anions and malondialdehyde (MDA), and weakened superoxide dismutase (SOD) activity, were all reversed by treatment with Ang-(1–7). Nox1 overexpression reversed the suppressing effects of Ang-(1–7) on paw swelling and arthritis scores in CIA rats. The Ang-(1–7)-induced improvement in spleen and thymus indexes in CIA rats was abolished by Nox1 overexpression. Nox1 overexpression reversed the inhibitory effects of Ang-(1–7) by increasing IL-1β, IL-6, TNF-α, and IFN-γ levels in the serum and hind paw of CIA rats. These results demonstrated that Nox1 increased the oxidative stress in arthritis, and Ang-(1–7) improved rheumatism in arthritis via inhibiting oxidative stress.

本研究旨在研究血管紧张素 (Ang)-(1-7) 在胶原诱导性关节炎 (CIA) 大鼠模型中的抗风湿作用和机制。CIA模型是使用雄性Wistar大鼠通过在尾部基部皮内注射完全弗氏佐剂中的牛胶原-II建立的。CIA 大鼠的血管紧张素转换酶 2 (ACE2)/Ang-(1-7)/Mas 受体 (MasR) 水平降低。通过注射 Ang-(1-7) 在 CIA 大鼠中完成爪肿胀和关节炎评分的减弱以及脾脏和胸腺指标的改善。Ang-(1– 7) 管理。此外，增强的 NADPH 氧化酶 (Nox) 活性，超氧阴离子和丙二醛 (MDA) 水平增加以及超氧化物歧化酶 (SOD) 活性减弱，都可以通过 Ang-(1-7) 处理逆转。Nox1 过表达逆转了 Ang-(1-7) 对 CIA 大鼠爪肿胀和关节炎评分的抑制作用。Nox1 过表达消除了 Ang-(1-7) 诱导的 CIA 大鼠脾脏和胸腺指数的改善。Nox1 过表达通过增加 CIA 大鼠血清和后爪中的 IL-1β、IL-6、TNF-α 和 IFN-γ 水平来逆转 Ang-(1-7) 的抑制作用。这些结果表明，Nox1 增加了关节炎的氧化应激，Ang-(1-7) 通过抑制氧化应激改善了关节炎的风湿病。Nox1 过表达逆转了 Ang-(1-7) 对 CIA 大鼠爪肿胀和关节炎评分的抑制作用。Nox1 过表达消除了 Ang-(1-7) 诱导的 CIA 大鼠脾脏和胸腺指数的改善。Nox1 过表达通过增加 CIA 大鼠血清和后爪中的 IL-1β、IL-6、TNF-α 和 IFN-γ 水平来逆转 Ang-(1-7) 的抑制作用。这些结果表明，Nox1 增加了关节炎的氧化应激，Ang-(1-7) 通过抑制氧化应激改善了关节炎的风湿病。Nox1 过表达逆转了 Ang-(1-7) 对 CIA 大鼠爪肿胀和关节炎评分的抑制作用。Nox1 过表达消除了 Ang-(1-7) 诱导的 CIA 大鼠脾脏和胸腺指数的改善。Nox1 过表达通过增加 CIA 大鼠血清和后爪中的 IL-1β、IL-6、TNF-α 和 IFN-γ 水平来逆转 Ang-(1-7) 的抑制作用。这些结果表明，Nox1 增加了关节炎的氧化应激，Ang-(1-7) 通过抑制氧化应激改善了关节炎的风湿病。CIA 大鼠血清和后爪中的 TNF-α 和 IFN-γ 水平。这些结果表明，Nox1 增加了关节炎的氧化应激，Ang-(1-7) 通过抑制氧化应激改善了关节炎的风湿病。CIA 大鼠血清和后爪中的 TNF-α 和 IFN-γ 水平。这些结果表明，Nox1 增加了关节炎的氧化应激，Ang-(1-7) 通过抑制氧化应激改善了关节炎的风湿病。