Effects of Shikonin on HIF-1α/VEGF Signaling Pathway in Mice with Acute Lung Injury Caused by Sepsis

Abstract

Sepsis often causes acute lung injury (ALI), a high-mortality complication. The HIF-1α/VEGF pathway plays a key role in sepsis, and shikonin, a natural compound with anti-inflammatory properties, may alleviate lung injury by targeting this pathway. Balb/c mice were randomly divided into four groups: sham group, model group, low-dose treatment group, and high-dose treatment group. The sham group underwent laparotomy without cecal ligation and puncture (CLP), while the model group underwent CLP to induce sepsis-related acute lung injury. After modeling, the low-dose and high-dose treatment groups received shikonin by gavage at doses of 12.5 mg/kg and 50 mg/kg, respectively, once daily for 14 days. The 7-day survival rate of the mice was monitored. Hematoxylin and eosin (HE) staining was used to assess lung tissue pathology, the lung wet/dry (W/D) weight ratio was measured, and a Western blot was performed to detect the expression of HIF-1α, VEGF, TNF-α, and IL-6 in lung tissue. Shikonin significantly improved the survival rate of septic mice, with the greatest effect observed in the high-dose group (p < 0.05). Compared with the model group, the lung W/D ratio and tissue damage in the shikonin-treated groups were significantly reduced in a dose-dependent manner. Additionally, shikonin significantly downregulated the expression of HIF-1α, VEGF, TNF-α, and IL-6, with the high-dose group showing the most pronounced reduction (p < 0.05). Shikonin alleviates acute lung injury in septic mice, potentially by inhibiting the expression of HIF-1α and reducing the production of related inflammatory factors.