锦葵素缓解脂多糖诱导的脓毒症急性肺损伤

Malvidin alleviates lipopolysaccharide-induced septic acute lung injury

目的 探讨锦葵素对脂多糖(LPS)诱导的脓毒症急性肺损伤(ALI)的潜在保护机制。方法 将30只雄性C57BL/6小鼠随机分为5组:对照组、LPS(10 mg/kg)组和锦葵素(5、10、20 mg/kg)+LPS组,每组6只。构建LPS诱导的脓毒症ALI小鼠模型。采用苏木精-伊红染色评估小鼠肺损伤情况,分别采用实时定量PCR法、生化试剂盒、TUNEL染色和透射电子显微镜(TEM)检测炎性反应、氧化应激反应和细胞凋亡情况。结果 LPS诱导的脓毒症ALI小鼠模型构建成功。与LPS组相比,锦葵素干预后小鼠肺肿胀程度明显减轻,肺组织中炎性细胞浸润得到缓解;支气管肺泡灌洗液中蛋白含量显著下降(P<0.05);肺组织中促炎性因子白细胞介素-6(IL-6)、IL-1β、肿瘤坏死因子-α(TNF-α)、诱导型一氧化氮合酶(iNOS) mRNA水平显著降低,而抗炎因子IL-10 mRNA水平显著升高(P<0.001);组织中抗氧化酶过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性显著升高(P<0.05),而过氧化产物丙二醛(MDA)含量则显著降低(P<0.001);组织中凋亡小体形成被抑制,TUNEL阳性细胞减少。结论 锦葵素对LPS诱导的脓毒症ALI具有保护作用,其机制涉及抑制炎症反应、缓解氧化应激和改善细胞凋亡,进而恢复肺组织形态异常和支气管肺泡完整性。

Objective To explore the potential protective mechanism of malvidin in lipopolysaccharide(LPS)-induced septic acute lung injury(ALI).Methods A total of 30 male C57BL/6 mice were randomly divided into five groups(n=6):a control group,a LPS(10 mg/kg)group,and malvidin(5,10,20 mg/kg)+LPS groups.A mouse model of LPS-induced septic ALI was established.Hematoxylin-eosin staining was used to assess lung injury in the mice.Real-time quantitative PCR,biochemical assay kits,TUNEL staining,and transmission electron microscopy(TEM)were used to evaluate inflammatory response,oxidative stress,and apoptosis,respectirely.Results The LPS-induced septic ALI mouse model was successfully established.Compared with mice in the LPS group,those treated with malvidin showed significantly reduced lung swelling and alleviated inflammatory cell infiltration in lung tissues.The protein content in bronchoalveolar lavage fluid significantly decreased(P<0.05).The mRNA levels of pro-inflammatory factors interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α),and inducible nitric oxide synthase(iNOS)in lung tissues significantly decreased,while the mRNA levels of the anti-inflammatory factor IL-10 significantly increased(P<0.001).The activities of antioxidant enzymes catalase(CAT),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)were significantly enhanced(P<0.05),while the content of the oxidative product malondialdehyde(MDA)was significantly reduced(P<0.001).Apoptotic body formation in the tissue was inhibited,and the number of TUNEL-positive cells was reduced.Conclusions Malvidin has protective effect on LPS-induced septic ALI.Its mechanism involves inhibiting the inflammatory response,alleviating oxidative stress,and improving apoptosis,thereby restoring abnormal lung tissue morphology and maintaining bronchoalveolar integrity.