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目的观察赤芍对内毒素(LPS)性急性肺损伤(ALI)时肺诱导型血红素氧化酶(HO-1)和诱导型一氧化氮合酶(iNOS)表达的影响,探讨其保护作用及分子机制。方法40只Wistar大鼠随机分为对照组、内毒素组(LPS组)、赤芍治疗组、赤芍预防组和血晶素组,每组8只。采用大鼠内毒素ALI模型,于LPS滴注后6h取动脉血行血气分析,测定肺组织中HO-1和iNOS的表达,肺泡灌洗液中性粒细胞比、蛋白含量,血清一氧化氮(NO)及肺组织丙二醛(MDA)含量,同时观察肺组织病理形态学改变。结果与对照组比较,LPS组HO-1和iNOS表达显著增强(P<0.01),肺泡灌洗液中性粒细胞比、蛋白含量、肺组织MDA和血清NO显著增加,而PaO2和HCO3ˉ明显降低(P<0.01);与LPS组比较,赤芍治疗组、赤芍预防组和血晶素组HO-1表达明显升高,而iNOS表达明显降低(P<0.05),病理学检查显示肺组织损伤程度较LPS组明显减轻。结论肺组织HO-1表达增强是内毒素性ALI的重要应激保护机制,赤芍对内毒素性ALI的防治作用可能与诱导HO-1的表达和抑制肺组织iNOS异常高表达有关。
Objective To observe the effect of Radix Paeoniae Rubra on the expression of lung-induced heme oxygenase (HO-1) and inducible nitric oxide synthase (iNOS) during endotoxin (LPS) acute lung injury (ALI), and to explore its protective effect. Molecular mechanism. Methods Forty Wistar rats were randomly divided into control group, endotoxin group (LPS group), Chishao treatment group, Chishao prevention group, and hemin group. There were 8 rats in each group. Using rat endotoxin ALI model, arterial blood was taken at 6h after LPS instillation for blood gas analysis to determine the expression of HO-1 and iNOS in lung tissue, the ratio of neutrophils in bronchoalveolar lavage fluid, protein content, serum nitric oxide ( NO) and malondialdehyde (MDA) content in lung tissue were observed. Pathological changes of lung tissue were also observed. Results Compared with the control group, the expression of HO-1 and iNOS in LPS group was significantly increased (P<0.01), the neutrophil ratio, protein content in lung lavage fluid, MDA in the lung tissue, and serum NO were significantly increased, while the PaO2 and HCO3 levels were significantly decreased. (P<0.01); Compared with LPS group, the expression of HO-1 was significantly increased in the Radix Paeoniae Radix group, the Radix Paeoniae Alba prevention group and hemin group, and the iNOS expression was significantly decreased (P<0.05). Pathological examination showed lung tissue. The degree of injury was significantly less than that in the LPS group. Conclusion The enhanced expression of HO-1 in lung tissue is an important protective mechanism of endotoxin-induced ALI. The preventive and therapeutic effects of Radix Paeoniae Rubra on endotoxin-induced ALI may be related to the induction of HO-1 expression and inhibition of the abnormally high expression of iNOS in lung tissue.