辣木叶多糖通过TLR4/NF-κB信号通路减轻横纹肌溶解致急性肾损伤

Moringa Leaf Polysaccharide Alleviates Cute Renal Injury Induced by Rhabdomyolysis Through TLR4/NF-κB Signaling Pathway

摘要:

为了探究辣木叶多糖（Moringa oleifera leaf polysaccharide，MLP）对横纹肌溶解致急性肾损伤（RM-AKI）的保护作用，并探索其潜在的作用机制。本研究通过建立小鼠RM-AKI模型和亚铁肌红蛋白诱导的肾小管上皮细胞（HK-2）损伤模型，使用生化试剂盒检测小鼠血清中肌酐（Cr）、尿素氮（BUN）、肌酸激酶（CK）以及肾脏组织中细胞因子（IL-1β、IL-6、TNF-α）的水平变化。此外，采用HE和TUNEL染色评估肾脏组织的病理学变化和细胞凋亡情况，Western blot分析肾组织及HK-2细胞中相关蛋白的表达。结果显示，与模型组相比，高剂量MLP处理的小鼠Cr、BUN、CK、IL-1β、IL-6和TNF-α的水平分别下降了67.87%、43.03%、21.39%、31.05%、54.20%和51.66%（P<0.001）。同时，肾小管上皮细胞的凋亡显著抑制，并有效降低了亚铁肌红蛋白诱导的HK-2细胞中的氧化应激水平。MLP显著下调了体内外TLR4、P-p65/p65以及Cleaved Caspase-3的蛋白表达。上述结果表明，MLP对横纹肌溶解致急性肾损伤具有明显的保护作用，为RM-AKI患者的临床治疗提供了科学依据。

Abstract:

The protective effect of Moringa oleifera leaf polysaccharide (Moringa oleifera leaf polysaccharide ,MLP) on rhabdomyolysis-induced acute kidney injury (RM-AKI) was investigated, and its potential mechanisms of action were explored.RM-AKI mice model and a ferrous myoglobin-induced renal tubular epithelial cell (HK-2) injury model were established. The levels of creatinine (Cr), blood urea nitrogen (BUN), creatine kinase (CK), and cytokines (IL-1β, IL-6, TNF-α) in the serum of mice and kidney tissues were measured using biochemical kits. Furthermore, histological changes and apoptosis in kidney tissues were assessed using hematoxylin and eosin (H&E) and TUNEL staining. Western blotting was employed to evaluate the expression of key proteins in both kidney tissues and HK-2 cells. The results revealed that, compared with the model group, the levels of Cr, BUN, CK, IL-1β, IL-6, and TNF-α in the high-dose MLP-treated mice decreased by 67.87%, 43.03%, 21.39%, 31.05%, 54.20%, and 51.66%, respectively (P<0.001). In parallel, apoptosis of renal tubular epithelial cells was significantly reduced, and oxidative stress levels in ferrous myoglobin-induced HK-2 cells were notably decreased. A significant downregulation in the protein expression of TLR4, P-p65/p65, and Cleaved Caspase-3 was induced by MLP treatment, both in vivo and in vitro. The above results indicate that Moringa oleifera leaf polysaccharide has a significant protective effect on acute kidney injury induced by rhabdomyolysis, which can provide a scientific basis for the treatment of clinical RM-AKI patients.