Department of Anesthesiology, Affiliated Foshan Hospital of SUN YAT-SEN University, Foshan, 528000, China.
Inflamm Res. 2017 May;66(5):399-411. doi: 10.1007/s00011-017-1023-9. Epub 2017 Feb 21.
Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury.
Acute kidney injury in mice was induced by cisplatin.
Mice were administered with DEX 25 μg/kg or atipamezole 250 μg/kg (once a day, for 3 days) after cisplatin treatment.
The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80 macrophages, CD3 T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction.
DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1β, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α adrenoceptor-dependent pathway.
We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.
顺铂为基础的化疗已广泛应用于癌症手术的围手术期，这加剧了肾损伤的风险。在这项研究中，我们研究了右美托咪定（DEX），一种常用的麻醉辅助剂，是否对顺铂诱导的急性肾损伤有保护作用。
通过顺铂诱导小鼠急性肾损伤。
顺铂处理后，小鼠给予 DEX25μg/kg 或 atipamezole250μg/kg（每天一次，连续 3 天）。
在顺铂给药后 72 小时评估肾功能和肾小管损伤评分。通过 TUNEL 检测法检测凋亡的肾小管细胞。通过免疫组织化学染色或 Western blot 检测 caspase-3、p53、Bax、F4/80 巨噬细胞、CD3T 细胞和 NF-κB。采用实时聚合酶链反应检测肾脏中的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6 和单核细胞趋化蛋白（MCP）-1。
DEX 处理可维持顺铂处理后小鼠的肾功能并降低肾小管损伤评分。DEX 处理的小鼠在顺铂损伤后凋亡的肾小管细胞较少，这与 Bax 减少以及 p53 和 caspase-3 的激活减少有关。DEX 抑制顺铂处理后巨噬细胞和 T 细胞浸润肾脏，这与 NF-κB 激活的抑制和 TNF-α、IL-1β、IL-6 和 MCP-1 的表达减少有关。此外，我们表明 DEX 赋予的肾保护作用可能与α肾上腺素能受体依赖途径有关。
我们证明 DEX 通过调节细胞凋亡和炎症反应来保护肾脏免受顺铂诱导的 AKI。
