Therapeutic effects of C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me; bardoxolone methyl) on radiation-induced lung inflammation and fibrosis in mice.
Therapeutic effects of C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me; bardoxolone methyl) on radiation-induced lung inflammation and fibrosis in mice.
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2-cyano-3,12-dioxolean-1,9-dien-28-oic 酸的 C-28 甲酯（CDDO-Me；巴多索隆甲基）对小鼠辐射诱导的肺部炎症和纤维化的治疗作用
DOI：
10.2147/dddt.s80958
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Zhou SF
中科院分区：
文献类型：
--
作者：
Wang YY;Zhang CY;Ma YQ;He ZX;Zhe H;Zhou SF
2-cyano-3,12-dioxoolean-1,9-dien-28-oic Acid (CDDO-Me) 的 C-28 甲酯是一种合成三萜类化合物，已被发现在体外和体内具有有效的抗炎和抗癌特性。然而，其在减轻辐射引起的肺损伤（RILI）（包括辐射引起的肺部炎症和纤维化）方面的有效性尚未经过测试。本研究的目的是探讨CDDO-Me对小鼠RILI的治疗作用及其潜在机制。在此，我们发现给予CDDO-Me可改善组织病理学评分，减少支气管肺泡灌洗液中炎症细胞的数量和总蛋白浓度，抑制促炎细胞因子（包括转化生长因子-β和白细胞介素-6）的分泌和表达，升高抗炎细胞因子白细胞介素-10的表达，并下调促纤维化基因的mRNA水平，包括纤连蛋白、α-平滑肌肌动蛋白和胶原蛋白I. CDDO-Me 减轻辐射引起的肺部炎症。 CDDO-Me 还降低了 Masson 三色染色评分、羟脯氨酸含量和促纤维化基因的 mRNA 水平，并阻止辐射诱导的胶原蛋白积累和纤维化。总的来说，这些发现表明 CDDO-Me 可以改善辐射引起的肺部炎症和纤维化，这种合成三萜类化合物是一种有前途的 RILI 新型治疗剂。需要进一步的机制、有效性和安全性研究来阐明 CDDO-Me 在 RILI 治疗中的作用。
The C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me), one of the synthetic triterpenoids, has been found to have potent anti-inflammatory and anticancer properties in vitro and in vivo. However, its usefulness in mitigating radiation-induced lung injury (RILI), including radiation-induced lung inflammation and fibrosis, has not been tested. The aim of this study was to explore the therapeutic effect of CDDO-Me on RILI in mice and the underlying mechanisms. Herein, we found that administration of CDDO-Me improved the histopathological score, reduced the number of inflammatory cells and concentrations of total protein in bronchoalveolar lavage fluid, suppressed secretion and expression of proinflammatory cytokines, including transforming growth factor-β and interleukin-6, elevated expression of the anti-inflammatory cytokine interleukin-10, and downregulated the mRNA level of profibrotic genes, including for fibronectin, α-smooth muscle actin, and collagen I. CDDO-Me attenuated radiation-induced lung inflammation. CDDO-Me also decreased the Masson’s trichrome stain score, hydroxyproline content, and mRNA level of profibrotic genes, and blocked radiation-induced collagen accumulation and fibrosis. Collectively, these findings suggest that CDDO-Me ameliorates radiation-induced lung inflammation and fibrosis, and this synthetic triterpenoid is a promising novel therapeutic agent for RILI. Further mechanistic, efficacy, and safety studies are warranted to elucidate the role of CDDO-Me in the management of RILI.