Protective Effect of Calcium Dobesilate on Induced AKI in Severely Burned Mice
Protective Effect of Calcium Dobesilate on Induced AKI in Severely Burned Mice
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羟苯磺酸钙对严重烧伤小鼠 AKI 的保护作用
DOI：
10.1159/000515420
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发表时间：
2021-06-14
期刊：
影响因子：
2.5
通讯作者：
Ren, Hong-qi
中科院分区：
文献类型：
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作者：
Akhter, Nazma;Sun, Hong;Ren, Hong-qi
背景：早期急性肾损伤(AKI)预示着严重烧伤患者的高死亡率。然而，严重烧伤所致早期AKI的病理生理学机制尚不清楚。本研究旨在观察羟苯磺酸钙(CAD)对严重烧伤小鼠早期AKI的保护作用，并探讨其作用机制。方法：将小鼠背部剃须浸泡在100℃水中10℃，造成S严重烧伤(总体表面积的40%)。CD-57雄性小鼠随机分为假手术组、烧伤组、烧伤+溶媒组、烧伤+CAD组。分别于伤后24、48h检测肾功能、肾小管上皮细胞活性、肾小管坏死及丝裂原活化蛋白激酶、蛋白激酶B和核因子-κB的磷酸化。分别于伤后24、48h对小鼠肾组织进行肾组织学、酶联免疫吸附试验、定量逆转录聚合酶链式反应和Western blotting检测，以探讨其作用机制。结果：烫伤组小鼠肾小管损伤、管型形成、血清肌酐、尿素氮及肾组织损伤分子1水平均明显升高，而CAD治疗组小鼠肾小管损伤明显减轻。此外，经CAD处理的小鼠肾脏组织中氧化还原电位和丙二醛水平降低，内源性抗氧化酶活性升高。烧伤小鼠肾脏AKT、p38、细胞外信号调节蛋白、Jun氨基末端激酶、核因子-κB信号转导活性升高，经冠脉介入治疗后基本恢复正常。结论：本研究首次证实了CAD对严重烧伤小鼠早期AKI的保护作用。CAD可能通过减轻肾脏氧化应激、细胞凋亡和炎症反应，调节肾脏某些信号通路发挥其保护作用。
Background: Early acute kidney injury (AKI) predicts a high mortality rate in severely burned patients. However, the pathophysiology of early AKI induced by severe burn has not been well-defined. This study was designed to examine the protective effects of calcium dobesilate (CaD) against severe burn-induced early AKI in mice and explore the mechanism. Methods: The shaved backs of mice were immersed in 100°C water for 10 s to make severe burn (40% of the total body surface area). CD-57 male mice were randomly divided into sham, burn, burn + vehicle, and burn + CaD groups. Renal function, reactive oxygen species generation, tubular necrosis, and phosphorylation of mitogen-activated protein kinase, protein kinase B (Akt), and nuclear factor (NF)-κB were measured at 24 and 48 h after the burn. Renal histology, ELISA, qRT-PCR, and Western blotting were performed on the renal tissue of mice to examine the effects and mechanisms at 24 and 48 h after the burn. Results: Tubular damage, cast formation, and elevations of serum creatinine, BUN, and renal tissue kidney injury molecule 1 levels were all observed in the burned mice, and these were all alleviated in the mice with CaD treatment. In addition, the levels of oxidation-reduction potential and malondialdehyde were decreased, while the activities of the endogenous antioxidative enzymes were increased in the kidney tissues from the mice after CaD treatment. Furthermore, the activities of Akt, p38, extracellular sign-regulated kinase, Jun N-terminal kinase, and NF-κB signaling were increased in the kidney of burned mice and normalized after CaD treatment. Conclusion: This study has established, for the first time, the protective effect of CaD against early AKI in severely burned mice. CaD may exert its protective effect through alleviating oxidative stress, apoptosis, and inflammation, as well as modulating some signaling pathways in the kidney.