槐定碱调节Hippo-YAP信号通路对急性呼吸窘迫综合征大鼠的改善作用  

The Improvement Effect of Sophoridine on Acute Respiratory Distress Syndrome in Rats by Regulating the Hippo-YAP Signaling Pathway

作　　者：李亚鹏[1] 李琴[1] 李莉[1] 陈燕君[1] 彭好[1] LI Yapeng;LI Qin;LI Li;CHEN Yanjun;PENG Hao(Suining Central Hospital,Suining Sichuan 629000,China)

机构地区：[1]遂宁市中心医院,四川遂宁629000

出　　处：《中医药导报》2024年第7期39-44,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：四川省医学(青年创新)科研课题计划项目(S19015)。

摘　　要：目的:探究槐定碱(SRI)对急性呼吸窘迫综合征(ARDS)大鼠的改善作用,并探究其作用机制。方法:随机取10只SD大鼠为空白组。50只SD大鼠采用脂多糖(LPS)气管滴注法构建ARDS大鼠模型。将造模成功大鼠随机分为模型组、SRI低剂量组、SRI中剂量组、SRI高剂量组、维替泊芬(Verteporfin)+SRI高剂量组,每组10只。造模2 h后SRI低、中、高剂量组分别予低(2 mg/kg)、中(6 mg/kg)、高(12 mg/kg)剂量SRI腹腔注射,Verteporfin+SRI高剂量组在腹腔注射Verteporfin(100 mg/kg)的基础上予SRI腹腔注射(12 mg/kg)。空白组和模型组腹腔注射等体积生理盐水。给药10 h后检测大鼠血氧分压(PaO_(2))、氧指数[PaO_(2)/吸入氧浓度(FiO_(2))]和肺湿/干(W/D)比,HE染色观察肺组织病理变化并进行病理损伤评分,酶联免疫吸附(ELISA)法检测肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和IL-10的水平,BCA检测BALF中总蛋白水平,姬姆萨染色检测BALF中巨噬细胞和中性粒细胞数量,ELISA法检测肺组织丙二醛(MDA),比色法检测肺组织超氧化物歧化酶(SOD)活性,荧光法检测肺组织髓过氧化物酶(MPO)活性,Western blotting检测肺组织Hippo-YAP通路蛋白表达。结果:与空白组比较,模型组大鼠肺组织结构破坏,大量炎症细胞浸润;与模型组比较,SRI低、中、高剂量组肺组织结构有所恢复;与SRI高剂量组比较,Verteporfin+SRI高剂量组肺组织损伤加重,肺泡肿胀、变性,炎症细胞浸润明显。模型组大鼠PaO_(2)、PaO_(2)/FiO_(2)值低于空白组,W/D比、病理损伤评分高于空白组(P<0.05);SRI低、中、高剂量组PaO_(2)、PaO_(2)/FiO_(2)值高于模型组,W/D比、病理损伤评分低于模型组(P<0.05);Verteporfin+SRI高剂量组PaO_(2)、PaO_(2)/FiO_(2)值低于SRI高剂量组,W/D比、病理损伤评分高于SRI高剂量组(P<0.05)。模型组大鼠BALF中TNF-α、IL-1β、IL-10、总蛋白水平及巨噬细胞计数、中性粒细胞计数高于空�Objective:To investigate the improvement effect of sophoridine(SRI)on acute respiratory distress syndrome(ARDS)in rats and its mechanism of action.Methods:Totally 10 SD rats were randomly selected as blank group.A total of 50 SD rats were constructed an ARDS rat model by lipopolysaccharide(LPS)tracheal infusion method.The successfully modeled rats were randomly divided into model group,low-dose SRI group,medium-dose SRI group,high-dose SRI group and Vitiporfin+high-dose SRI group,with 10 rats in each group.After 2 hours of modeling,the low,medium and high-dose SRI groups were given intraperitoneal injections of low(2 mg/kg),medium(6 mg/kg)and high(12 mg/kg)doses of SRI,respectively.The Verteporfin+high-dose SRI group was given intraperitoneal injections of SRI(12 mg/kg)on the basis of intraperitoneal injections of Verteporfin(100 mg/kg).The blank group and model group were intraperitoneally injected with an equal volume of physiological saline.The blood oxygen partial pressure(PaO_(2)),PaO_(2)/inhaled oxygen concentration(FiO_(2)),and lung wet/dry(W/D)ratio were measured in 10 hours.Hematoxylin-eosin staining was applied to observe pathological changes in lung tissue and score pathological injury,and enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-10 in alveolar lavage fluid(BALF).BCA was applied to detect total protein levels in BALF.Giemsa staining was applied to detect the numbers of macrophages and neutrophils in BALF.MDA was detected by ELISA,and SOD was detected by colorimetry.MPO activity was detected by fluorescence.Western blotting was applied to detect the expression of Hippo-YAP pathway proteins.Results:Compared with the blank group,the lung tissue structure was destroyed in the model group and a large number of inflammatory cells infiltrated.Compared with the model group,the lung tissue structure recovered in low,medium and high-dose SRI groups.Compared with high-dose SRI group,Verteporfin+high-dose SRI group sh

关 键 词：急性呼吸窘迫综合征 槐定碱 肺损伤 Hippo-YAP信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]