Anisodamine hydrobromide (AniHBr) is a Chinese medicine used to treat septic shock. However, whether AniHBr could ameliorate septic acute kidney injury and the underlying mechanism were not investigated. In the present study, 18 male Sprague-Dawley rats (200-250 g) were randomly divided into control, lipopolysaccharide (LPS) and LPS+AniHBr groups. Rats were intravenously administrated with LPS or normal saline (for control). After 4 h, the rats were intravenously administrated with AniHBr (LPS+AniHBr) or normal saline at 4 h intervals. Hemodynamic parameters including blood pressure and heart rate were measured. The histopathologic evaluation of kidney tissues was performed. Lactate, creatine kinase, inflammatory cytokines and oxidative stress indicators were determined. Using Seahorse analysis, the metabolic analysis of mitochondrial stress and glycolytic stress in human renal proximal tubular epithelial cells treated with TNF-α in the presence of AniHBr was performed. AniHBr administration significantly reduced serum creatine kinase and lactate following LPS treatment. AniHBr significantly improved hemodynamics in sepsis rats including increase in the mean atrial pressure and reduction in the heart rate. AniHBr significantly attenuated LPS-induced TNF-α, IL-6 and IL-1β in serum, and LPS-induced TNF-α and IL-1β in renal tissues. The LPS-reduced SOD activity and LPS-increased MDA content were reversed by AniHBr. In vitro, TNF-α increased mitochondrial oxygen consumption and glycolysis, but inhibited the ATP generation, which was reversed by AniHBr. Thus, AniHBr protects against the LPS-induced inflammatory cytokines, mitochondrial dysfunction and oxidative stress, and thus attenuates the LPS-induced acute kidney injury, showing AniHBr is a promising therapeutic drug for septic kidney injury.

中文翻译：

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氢溴酸山iso碱对脂多糖诱导的急性肾脏损伤的保护作用。

氢溴酸山iso碱（AniHBr）是用于治疗败血性休克的中药。但是，AniHBr是否可以减轻败血性急性肾脏损伤及其潜在机制尚未进行研究。在本研究中，将18只雄性Sprague-Dawley大鼠（200-250 g）随机分为对照组，脂多糖（LPS）和LPS + AniHBr组。给大鼠静脉内施用LPS或生理盐水（作为对照）。4小时后，以4小时间隔静脉内给大鼠静脉内施用AniHBr（LPS + AniHBr）或生理盐水。测量了包括血压和心率在内的血液动力学参数。进行肾脏组织的组织病理学评估。测定了乳酸，肌酸激酶，炎性细胞因子和氧化应激指标。使用Seahorse分析，在AniHBr存在下，对TNF-α处理的人肾近端肾小管上皮细胞线粒体应激和糖酵解应激的代谢分析。在进行LPS治疗后，给予AniHBr可以显着降低血清肌酸激酶和乳酸。AniHBr明显改善了败血症大鼠的血流动力学，包括平均心房压升高和心率降低。AniHBr显着减弱了LPS诱导的血清TNF-α，IL-6和IL-1β，以及LPS诱导的肾组织的TNF-α和IL-1β。AniHBr可逆转LPS降低的SOD活性和LPS增加的MDA含量。在体外，TNF-α增加了线粒体耗氧量和糖酵解，但抑制了ATP的产生，这被AniHBr逆转。因此，AniHBr可以抵抗LPS诱导的炎症细胞因子，