黄芪甲苷通过HMGB1/NF-κB通路减轻脓毒症大鼠相关肺损伤

Astragaloside Ⅳ alleviates sepsis-related lung injury through the HMGB1/NF- κB pathway in rats

目的 探讨黄芪甲苷(AS-Ⅳ)对脓毒症大鼠肺损伤的影响及其可能作用机制。方法 选取48只大鼠采用盲肠结扎穿孔法建立脓毒症大鼠模型,造模成功大鼠随机分为模型组、AS-Ⅳ低、中和高剂量(20、40、80 mg/kg)组,各12只,另设对照组12只。记录各组大鼠肺湿/干质量比值(W/D);ELISA法检测各组大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平;HE染色观察各组大鼠肺组织病理变化,评定大鼠肺组织损伤情况;RT-qPCR和Western blot分别检测大鼠肺组织中高迁移率族蛋白B1(HMGB1)、核因子-κB p65(NF-κB p65)及其磷酸化mRNA和蛋白表达情况。结果 与模型组比较,AS-Ⅳ低、中、高剂量组大鼠肺组织W/D、TNF-α、IL-1β、IL-6、肺组织病理学评分、HMGB1和NF-κB p65 mRNA水平、HMGB1和p-NF-κB p65蛋白表达水平均降低(P<0.05),以AS-Ⅳ高剂量组效果最佳。结论 AS-Ⅳ能够改善脓毒症大鼠肺组织损伤,减轻炎症反应,可能是通过抑制HMGB1/NF-κB通路,减少NF-κB p65磷酸化蛋白表达发挥作用。

Objective To investigate the effect of astragaloside Ⅳ(AS-Ⅳ) on lung injury in septic rats and its possible mechanism. Methods A total of 48 rats were randomly divided into model group, low-dose, medium-dose and high-dose AS-Ⅳ(20, 40, 80 mg/kg) groups(n=12 each) and control group(n=12). The lung wet/dry weight ratio(W/D) was recorded. The serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were detected by ELISA. HE staining was used to observe the pathological changes of lung tissue of rats in each group, and to evaluate the lung tissue injury of rats. RT-qPCR and Western blot were used to detect the expression of high mobility group protein B1(HMGB1), nuclear factor-κB p65(NF-κB p65), and its phosphorylated mRNA and protein in lung tissue of rats. Results Compared with the model group, the W/D, TNF-α, IL-1β, IL-6, lung histopathological score, mRNA levels of HMGB1 and NF-κB p65, protein expression levels of HMGB1 and p-NF-κB p65 in the lung tissue of rats in the low-dose, medium-dose, and high-dose AS-Ⅳ groups were decreased(P<0.05), and AS-Ⅳ high dose group had the best effect. Conclusion AS-Ⅳ can alleviate lung tissue injury and reduce inflammation in septic rats, possibly by inhibiting the HMGB1/NF-κB pathway and reducing the expression of NF-κB p65 phosphorylated protein.