Department of Nephrology, Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, Xiamen, China.
Department of Pediatrics, The First Affiliated Hospital of Xiamen University, Xiamen, China.
PLoS One. 2024 Aug 23;19(8):e0308557. doi: 10.1371/journal.pone.0308557. eCollection 2024.
To investigate the effect of dexamethasone (DXM) on acute lung and kidney injury with sepsis and its possible mechanism.
Control (NC), lipopolysaccharide (LPS) and lipopolysaccharide + dexamethasone (LPS+DXM) treated groups were established by random assignment of 72 Wistar rats. The NC rats were injected with physiological saline, while the LPS group was injected with LPS (5 mg/kg) and LPS+DXM group was injected with LPS(5 mg/kg) first and followed by DXM (1 mg/kg). Serum tumor necrosis factor-α (TNF-α) and serum macrophage inflammatory protein 1α (MIP-1α) were measured by ELISA. Lung wet/dry weight ratio, serum creatinine(SCR) and blood urea nitrogen(BUN) were determined at various time points. Hematoxylin Eosin staining (HE) for pathological changes in the lung and kidney. Radioimmunoassay was used to detect the levels of angiotensin II (Ang II) in plasma, lung and kidney tissues. Immunohistochemistry and western blot (WB) were used to detect angiotensin II receptor type 1 (AT1R) protein and angiotensin II receptor type 2 (AT2R) protein in lung and kidney tissues. The level of nitric oxide (NO) in serum, lung and kidney were detected using nitrate reductase method.
Compared with control group, serum TNF-α, MIP-1α, SCR, BUN, lung W/D, Ang II level in plasma, lung and kidney, lung and kidney AT2R protein, NO level in serum, lung and kidney were significantly elevated(P<0.05) and pathological damage of lung and kidney tissues were showed in LPS group rats (P<0.05), whereas DXM down-regulated the above indexes and alleviate pathological damage of lung and kidney tissues. However, the expression of the lung and kidney AT1R protein was opposite to the above results.
Sepsis can cause acute lung and kidney injury and changes RAAS components in circulating, lung and renal. DXM can improve acute lung and kidney injury in septic rats, and the mechanism may be related to the down-regulation of inflammatory factors, AngII, AT2R, NO and up-regulation of AT1R expression by DXM.
研究地塞米松（DXM）对脓毒症急性肺肾损伤的作用及其可能机制。
将 72 只 Wistar 大鼠随机分为对照组（NC）、脂多糖（LPS）组和脂多糖+地塞米松（LPS+DXM）组。NC 大鼠注射生理盐水，LPS 组大鼠注射 LPS（5mg/kg），LPS+DXM 组大鼠先注射 LPS（5mg/kg），再注射 DXM（1mg/kg）。采用酶联免疫吸附试验（ELISA）检测血清肿瘤坏死因子-α（TNF-α）和血清巨噬细胞炎症蛋白 1α（MIP-1α）。在不同时间点测定肺湿/干重比、血清肌酐（SCR）和血尿素氮（BUN）。苏木精-伊红染色（HE）观察肺和肾组织的病理变化。放射免疫法检测血浆、肺、肾组织中血管紧张素 II（Ang II）的水平。免疫组化和蛋白质印迹法（WB）检测肺、肾组织中血管紧张素 II 受体 1 型（AT1R）和血管紧张素 II 受体 2 型（AT2R）蛋白。硝酸还原酶法检测血清、肺、肾组织中一氧化氮（NO）的水平。
与对照组相比，LPS 组大鼠血清 TNF-α、MIP-1α、SCR、BUN、肺湿/干重比、血浆、肺、肾组织中 Ang II 水平、肺、肾组织中 AT2R 蛋白、血清、肺、肾组织中 NO 水平均明显升高（P<0.05），肺、肾组织病理损伤明显（P<0.05），而 DXM 则下调上述指标，减轻肺、肾组织病理损伤。然而，肺、肾组织中 AT1R 蛋白的表达则与上述结果相反。
脓毒症可引起急性肺肾损伤，并改变循环、肺和肾组织中的 RAAS 成分。DXM 可改善脓毒症大鼠的急性肺肾损伤，其机制可能与 DXM 下调炎症因子、AngII、AT2R、NO，上调 AT1R 表达有关。
