Data Sheet 1_Modulatory role of Spirulina platensis in oxidative stress, apoptosis, and gene expression in a rat model of dexamethasone-induced hepatotoxicity.pdf

The rising prevalence of hyperlipidemia and hepatic disorders has intensified interest in the therapeutic use of functional foods and botanical drugs. Spirulina platensis, a blue-green microalga, is known for its antioxidant, anti-inflammatory, and lipid-lowering properties. However, its potential hepatoprotective effects, particularly against glucocorticoid-induced liver damage, remain underexplored. This study aimed to investigate the protective effects of Spirulina platensis aqueous extract (SPAE) against dexamethasone (DEX)-induced oxidative stress, lipid dysregulation, apoptosis, hepatic injury, and associated gene expression changes in male rats. Forty male albino rats (150 ± 10 g) were randomly divided into four groups (n = 10). The control group received a standard diet and saline for 28 days. The second group was intraperitoneally injected with DEX (10 mg/kg) on alternate days for 28 days to induce hepatic and oxidative damage. The third and fourth groups were co-administered DEX with SPAE at 400 mg/kg and 800 mg/kg body weight/day orally for the same period. At the end of the experiment, key physiological and biochemical parameters were assessed, including feed intake, body weight gain, feed efficiency ratio (FER), and liver weight. Blood lipid profiles, liver enzymes (ALT, AST, ALP), total and direct bilirubin, and serum protein levels were analyzed. Additionally, antioxidant enzyme activities (SOD, CAT), markers of lipid peroxidation (MDA, NO), and mRNA expression levels of genes related to oxidative stress (Nrf2, SOD2), apoptosis (Bax, Bcl-2), lipid metabolism (PPAR-α), and DNA damage (p53) were evaluated using quantitative RT-PCR. SPAE treatment also modulated upstream regulators Keap1 and AMPK, supporting activation of the Nrf2 and PPAR-α pathways. The results revealed that SPAE significantly ameliorated DEX-induced hyperlipidemia, hepatic dysfunction, oxidative stress, and abnormal gene expression profiles, with the 800 mg/kg dose showing superior efficacy. These findings suggest that Spirulina platensis aqueous extract offers a promising protective effect against glucocorticoid-induced metabolic and hepatic disturbances, potentially through its antioxidant, anti-apoptotic, and gene-regulatory properties.

高脂血症与肝脏疾病的患病率持续攀升，使得功能性食品及植物药的治疗应用愈发受到学界关注。钝顶螺旋藻（Spirulina platensis）作为一种蓝绿色微藻，因具备抗氧化、抗炎及调脂活性而广为人知。然而其潜在的肝保护作用，尤其是针对糖皮质激素诱导肝损伤的相关研究仍有待深入探索。

本研究旨在探讨钝顶螺旋藻水提物（Spirulina platensis aqueous extract, SPAE）对雄性大鼠地塞米松（dexamethasone, DEX）诱导的氧化应激、脂质代谢紊乱、细胞凋亡、肝损伤及相关基因表达变化的保护作用。

选取40只体重为150±10 g的雄性白化大鼠，随机分为4组，每组10只。对照组饲喂标准饲料并腹腔注射生理盐水，干预周期为28天。第二组隔日腹腔注射10 mg/kg的地塞米松，持续28天以构建肝损伤与氧化应激模型。第三、第四组在给予地塞米松的同时，分别经口灌胃400 mg/(kg·d)与800 mg/(kg·d)体重的SPAE，干预周期与前述一致。

实验结束后，检测多项核心生理与生化指标：包括摄食量、体重增重、饲料效率比（FER）及肝脏重量。分析血液脂质谱、肝酶（丙氨酸氨基转移酶ALT、天冬氨酸氨基转移酶AST、碱性磷酸酶ALP）、总胆红素与直接胆红素、血清蛋白水平。此外，采用定量实时反转录PCR（qRT-PCR）检测抗氧化酶活性（超氧化物歧化酶SOD、过氧化氢酶CAT）、脂质过氧化标志物（丙二醛MDA、一氧化氮NO），以及与氧化应激（核因子E2相关因子2 Nrf2、超氧化物歧化酶2 SOD2）、细胞凋亡（Bax、Bcl-2）、脂质代谢（过氧化物酶体增殖物激活受体α PPAR-α）和DNA损伤（p53）相关基因的mRNA表达水平。SPAE还可调控上游调控因子Kelch样ECH相关蛋白1（Keap1）与腺苷酸活化蛋白激酶（AMPK），进而激活Nrf2及PPAR-α通路。

研究结果显示，SPAE可显著改善地塞米松诱导的高脂血症、肝功能异常、氧化应激及异常基因表达谱，其中800 mg/kg剂量的干预效果更为优异。本研究结果表明，钝顶螺旋藻水提物对糖皮质激素诱导的代谢紊乱与肝损伤具有良好的保护潜力，其作用机制可能与其抗氧化、抗凋亡及基因调控特性相关。