Department of Nephrology, The First Affiliated Hospital of Changde Vocational Technical College, Changde, China.
Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China,
Nephron. 2019;142(3):243-252. doi: 10.1159/000497821. Epub 2019 Mar 6.
Focal segmental glomerulosclerosis (FSGS) is a common histologic pattern of kidney injury, which may eventually lead to end-stage renal disease.
Salidroside (SAL, p-hydroxyphenyl-β-D-glucoside) is an active component isolated from Rhodiolarosea, which has various pharmacological properties including anti-inflammation and antioxidation. SAL may attenuate FSGS, but the underlying mechanism is not clear. Thus, in this study, we focus on the renoprotective role of SAL in FSGS using Adriamycin nephropathy (AN) mouse models.
In C57 BL/6 mice, AN was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then they were organized into 6 groups for the animal experiments: AN + saline group; AN + SAL group (40 mg/kg); AN + LY294002 (a selective phosphatidylinositol 3-kinase [PI3K] inhibitors, 50 mg/kg) group; AN + SAL + LY294002 group; AN + YC-1 (a selective hypoxia-inducible factor-1α [HIF-1α] inhibitors, 50 mg/kg) group; and AN + SAL + YC-1 group. All of the drugs were given on the day of Adriamycin injection and continued for 6 weeks, and the drugs were given by intraperitoneally. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis.
In FSGS mouse models, SAL treatment could ameliorate proteinuria, renal function, and markers of Nephrotic Syndrome inhibit alpha-smooth muscle actin and fibronectin expression and downregulates the expression of HIF-1α. Besides, the levels of PI3K and p-protein kinase B (Akt) in renal tissues were significantly decreased after SAL injection. Eventually, SAL treatment results reduced inflammatory cytokines and reactive oxygen species production.
In summary, SAL ameliorates FSGS mainly by inhibiting the expression of HIF-1α through PI3K/Akt pathway, which might offer an array of hope for ameliorating FSGS.
局灶节段性肾小球硬化症（FSGS）是一种常见的肾脏损伤组织学模式，最终可能导致终末期肾病。
红景天苷（SAL，对-羟基苯-β-D-葡萄糖苷）是从红景天中分离出来的一种活性成分，具有多种药理特性，包括抗炎和抗氧化作用。SAL 可能减轻 FSGS，但作用机制尚不清楚。因此，在这项研究中，我们使用阿霉素肾病（AN）小鼠模型关注 SAL 在 FSGS 中的肾保护作用。
在 C57BL/6 小鼠中，通过尾静脉在第 0 天用阿霉素（10mg/kg 体重，溶于生理盐水）诱导 AN。然后，他们被组织成 6 组进行动物实验：AN+生理盐水组；AN+SAL 组（40mg/kg）；AN+LY294002 组（一种选择性磷脂酰肌醇 3-激酶[PI3K]抑制剂，50mg/kg）；AN+SAL+LY294002 组；AN+YC-1 组（一种选择性低氧诱导因子-1α [HIF-1α]抑制剂，50mg/kg）；和 AN+SAL+YC-1 组。所有药物均在阿霉素注射当天给予，并持续 6 周，通过腹腔内给药。6 周后，处死小鼠；收集肾脏和血液样本进行进一步分析。
在 FSGS 小鼠模型中，SAL 治疗可改善蛋白尿、肾功能和肾病综合征标志物抑制α-平滑肌肌动蛋白和纤维连接蛋白的表达，并下调 HIF-1α 的表达。此外，SAL 注射后肾脏组织中 PI3K 和 p-蛋白激酶 B（Akt）的水平明显降低。最终，SAL 治疗可减少炎症细胞因子和活性氧的产生。
总之，SAL 通过 PI3K/Akt 通路抑制 HIF-1α 的表达来改善 FSGS，这可能为改善 FSGS 提供了一系列希望。
