羟基红花黄色素A对小鼠重症急性胰腺炎相关肺损伤的保护作用研究

Protective effect of hydroxysafflor yellow A on lung injury associated with severe acute pancreatitis in mice

目的本文研究羟基红花黄色素A(Hydroxysafflor yellow A,HSYA)对重症急性胰腺炎(severe acute pancreatitis,SAP)相关肺损伤的保护作用及其机制。方法50只小鼠随机数字法分成5组(每组10只):假手术组,SAP组和不同剂量(20,40和80 mg/kg)HSYA预处理组。在SAP诱导前24 h,采用HSYA预处理小鼠,并在造模72 h后分离胰腺和肺组织用于组织病理学检查,并收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)用于生化分析。结果与对照组相比,SAP组血清淀粉酶活性、肺损伤病理评分和BALF蛋白浓度均显著增高[(2120.44±354.5)U/L vs.(226.72±20.84)U/L;(6.91±0.28)vs.(0.53±0.18);(2563.25±348.22)μg/mL vs.(345.62±56.35)μg/mL,均P<0.05];炎性因子tumor necrosis factor(TNF)-α和interleukin(IL)-6水平和髓过氧化物酶(myeloperoxidase,MPO)活性升高[(120.5±14.25)pg/mL vs.(31.5±4.82)pg/mL;(214.72±10.62)pg/mL vs.(39.26±5.66)pg/mL;(4.52±0.34)Units/mg vs.(1.03±0.17)Units/mg]。与SAP组相比,HSYA预处理显著减轻SAP相关胰腺和肺组织损伤以及BALF中炎性因子TNF-α、IL-6和MPO活性。此外,HSYA促进抗氧化蛋白血红素氧合酶1(heme oxygenase-1,HO-1)表达,并阻断NF-κB信号通路激活。结论HSYA可以发挥抗炎和抗氧化活性从而抑制SAP相关肺损伤,表明HSYA可能是SAP诱导肺损伤的潜在治疗药物。

Objective To investigate the protective effect and mechanism of hydroxysafflor yellow A(HSYA)on severe acute pancreatitis(SAP)related lung injury.Methods Fifty mice were randomly(random number)divided into five groups:the sham-operated group,SAP group and different doses(20,40 and 80 mg/kg)of HSYA pretreatment group.Mice were pretreated with HSYA 24 h before SAP induction,pancreatic and lung tissues were isolated for histopathological examination at 72 h after modeling,and bronchoalveolar lavage fluid(BALF)was collected for biochemical analysis.Results Compared with the sham-operated group,serum amylase activity,lung injury pathological score and BALF protein concentration in the SAP group were significantly increased[(2120.44±354.50)U/L vs.(226.72±20.84)U/L;(6.91±0.28)vs.(0.53±0.18);(2563.25±348.22)pg/mL vs.(345.62±56.35)pg/mL,all P<0.05].Inflammatory factors tumor necrosis factor(TNF)-α and interleukin(DL)-6 levels and myeloperoxidase(MPO)activity were increased[(120.5±14.25)pg/mL vs.(31.5±4.82)pg/mL;(214.72±10.62)pg/mL vs.(39.26±5.66)pg/mL;(4.52±0.34)U/mg vs.(1.03±0.17)U/mg].Compared with the SAP group,HSYA pretreatment significantly attenuated SAP-related pancreatic and lung tissue damage and the activities of the inflammatory factors TNF-α,IL-6 and MPO in BALF.In addition,HSYA promoted the expression of the antioxidant protein heme oxygenase-1 and blocked the activation of the NF-κB signaling pathway.Conclusions HSYA exerts anti-inflammatory and antioxidant activities to inhibit SAP-related lung injury,which indicated that HSYA may be a potential therapeutic drug for SAP-induced lung injury.