Salvianolic acid A (SAA) is a minor phenolic carboxylic acid extracted from Salviae miltiorrhizae Bunge (Danshen). SAA exhibits a variety of pharmacological activities, such as antioxidative, anti-thrombotic, neuroprotective, and anti-fibrotic effects, as well as protection from myocardial ischemia and prevention of diabetes and other diseases. Furthermore, SAA has shown renal-protective effects in doxorubicin-induced nephropathy. However, there has been limited research regarding the effects of SAA and underlying mechanisms in chronic kidney disease (CKD). Here, we examined the effects and molecular mechanisms of SAA in an established animal model of 5/6 nephrectomized (5/6Nx) rats. The rats were injected with SAA (2.5, 5, and 10 mg/kg per day, intraperitoneally (ip)) for 28 days. SAA dose-dependently lowered the levels of urine protein, blood urea nitrogen, serum creatinine, plasma total cholesterol, and plasma triglycerides in 5/6Nx rats. Histological examination revealed that SAA dose-dependently attenuated renal pathological lesions, evidenced by reduced renal tubulointerstitial fibrosis by decreasing the expression levels of tumor growth factor-β1 and α-smooth muscle actin in 5/6Nx rats. Moreover, SAA dose-dependently inhibited the activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, subsequently attenuating the secretion of tumor necrosis factor-α and interleukin-1β and inhibiting the expression of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in kidneys of 5/6Nx rats. The above results were consistent with those obtained in lipopolysaccharide-induced HK-2 cells in vitro (a recognized in vitro inflammatory model). In conclusion, our results demonstrated that SAA effectively attenuates kidney injury in 5/6Nx rats. The therapeutic effects of SAA on kidney injury can be attributed to its anti-inflammatory activities through inhibition of the activation of the NF-κB and p38 MAPK signaling pathways.

中文翻译：

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丹酚酸A通过抑制5/6肾切除大鼠的NF-κB和p38 MAPK信号通路来减轻肾脏损伤和炎症。

丹酚酸A（SAA）是从丹参丹参（丹参）中提取的少量酚羧酸。SAA表现出多种药理活性，例如抗氧化，抗血栓形成，神经保护和抗纤维化作用，以及防止心肌缺血和预防糖尿病及其他疾病的作用。此外，SAA在阿霉素诱导的肾病中显示出肾脏保护作用。但是，关于SAA的作用及其在慢性肾脏病（CKD）中的潜在机制的研究还很有限。在这里，我们检查了建立的5/6肾切除（5 / 6Nx）大鼠的动物模型中SAA的作用和分子机制。给大鼠注射SAA（每天2.5、5和10 mg / kg，腹膜内（ip））28天。SAA剂量依赖性地降低了尿蛋白的水平，5 / 6Nx大鼠的血尿素氮，血清肌酐，血浆总胆固醇和血浆甘油三酸酯。组织学检查显示，SAA剂量依赖性地减轻了肾脏病理病变，这通过降低5 / 6Nx大鼠肿瘤生长因子-β1和α-平滑肌肌动蛋白的表达水平而减轻了肾小管间质纤维化所证明。此外，SAA剂量依赖性地抑制核因子-κB（NF-κB）和p38丝裂原激活的蛋白激酶（MAPK）信号通路的激活，从而减弱肿瘤坏死因子-α和白介素-1β的分泌并抑制其表达。 5 / 6Nx大鼠肾脏中单核细胞趋化蛋白-1，细胞间黏附分子-1和血管细胞黏附分子-1的变化 上述结果与在体外脂多糖诱导的HK-2细胞（公认的体外炎症模型）中获得的结果一致。总之，我们的结果表明，SAA可有效减轻5 / 6Nx大鼠的肾脏损伤。SAA对肾脏损伤的治疗作用可归因于其抗炎活性，可通过抑制NF-κB和p38 MAPK信号通路的激活来实现。