羟基红花黄素A对脑卒中相关性肺炎大鼠肺组织的保护作用及机制  

Protective effects of hydroxysafflor yellow A on lung tissues of stroke-associated pneumonia rats

作　　者：王涛[1] 刘宏祥[1] 齐姣[1] 史小盼[1] 王珍[1] 刘一[1] 闫丽静 WANG Tao;LIU Hongxiang;QI Jiao;SHI Xiaopan;WANG Zhen;LIU Yi;YAN Lijing(The Affiliated Hospital of Hebei University,Baoding 071000,China)

机构地区：[1]河北大学附属医院,河北保定071000

出　　处：《山东医药》2018年第37期11-15,共5页Shandong Medical Journal

基　　金：河北省科技计划项目(132777203)

摘　　要：目的探讨羟基红花黄素A(HSYA)对脑卒中相关性肺炎(SAP)大鼠肺组织的保护作用及可能的机制。方法随机选取SD大鼠10只作为假手术组,其余大鼠采用四动脉阻断法制备SAP模型。将造模成功的SAP模型大鼠随机分为4组,分别用生理盐水(假手术组、SAP组)、Janus激酶2特异性抑制剂N-苄基-3,4-二羟基亚苄基氰基乙酰胺(AG490,5 mg/kg,AG490组)、低剂量(8 mg/kg,L-HSYA组)及高剂量HSYA(16 mg/kg,H-HSYA组)对大鼠进行治疗,连续给药7 d。用HE染色法观察各组肺组织病理变化;测量肺组织湿重量(W)、干重量(D),计算W/D值;用比色法检测肺组织中髓过氧化物酶(MPO)活性;用酶联免疫吸附法检测支气管肺泡灌洗液(BALF)中炎性细胞因子水平及肺组织核提取物中核因子κB(NF-κB)结合活性; Western blotting法检测肺组织核提取物中磷酸化Janus激酶2(p-JAK2)、磷酸化信号传导子及转录激活子3(p-STAT3)、核因子κB p65(NF-κB p65)蛋白表达。结果与假手术组比较,SAP组肺损伤评分、肺组织W/D值、MPO活性高,BALF中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-18水平及NF-κB DNA结合活性高,NF-κB p65、p-JAK2、p-STAT3蛋白表达高(P均<0. 05);与SAP组比较,AG490组、L-HSYA组及H-HSYA组肺损伤评分、肺组织W/D值、MPO活性低,BALF中TNF-α、IL-1β、IL-18水平及NF-κB DNA结合活性低,NF-κB p65、p-JAK2、p-STAT3蛋白表达低(P均<0. 05);且AG490组、HHSYA组以上指标变化最明显(P均<0. 05)。结论 HSYA能够减轻SAP大鼠肺组织的损伤及炎症反应,该作用可能与抑制肺组织中JAK2/STAT3信号通路激活有关。Objective To investigate the protective effect of hydroxysafflor yellow A(HSYA)on lung tissues of stroke-associated pneumonia(SAP)rats and to explore its possible mechanism.Methods Ten SD rats were randomly selected as the sham operation group,and the other rats were prepared for the SAP models by 4-artery occlusion method.After modeling,the rats were treated with normal saline(sham group,SAP group),Janus kinase 2(JAK2)specific inhibitor N-benzyl-3,4-two hydroxybenzyl cyanoacetamide AG490(5 mg/kg,AG490 group),low-dose HSYA(8 mg/kg L-HSYA group)and high-dose HSYA(16 mg/kg,H-HSYA group)for 7 consecutive days.Histopathological analysis was used to observe the lung injury.We measured the wet weight(W)and dry weight(D)of the lung tissue and calculated the W/D value.The activity of myeloperoxidase(MPO)in the lung tissues was detected by colorimetry.The level of inflammatory cytokines in bronchoalveolar lavage fluid(BALF)was detected by enzyme-linked immunosorbent assay.Enzyme linked immunosorbent assay was used to detect nuclear factorκB(NF-κB)binding activity in the lung tissues.Western blotting was used to analyze the expression of phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3),nuclear factorκB p65(NF-κB p65)in the nuclear extracts of the lung tissues.Results Compared with the sham group,the lung injury score,the W/D,MPO of the lung tissues,the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-18 in BALF,the activity of NF-κB in p65 subunit,and the expression of p-JAK2 and p-STAT3 protein in the SAP group increased significantly(all P<0.05).Compared with the SAP group,the lung injury score,the W/D of the lung tissues,the levels of TNF-α,IL-1β,and IL-18 in BALF,the activity of NF-κB in p65 subunit,and the expression of p-JAK2 and p-STAT3 protein decreased significantly in the AG490 group,L-HSYA group and H-HSYA group(all P<0.05).Conclusion HSYA can attenuate the lung tissue damage and inflammatory response in SAP rats,whi

关 键 词：肺炎 脑卒中 羟基红花黄素A JAK2/STAT3信号通路 

分 类 号：R743.33[医药卫生—神经病学与精神病学]