芹菜素预处理对脓毒症大鼠急性肺损伤的保护作用及机制研究  

Protective effect and mechanism of apigenin pretreatment on acute lung injury in septic rats

作　　者：崔卫正[1] 刘爽[1] CUI Weizheng;LIU Shuang(Handan Central Hospital, Handan 056001, Hebei, China)

机构地区：[1]邯郸市中心医院,河北邯郸056001

出　　处：《现代中西医结合杂志》2021年第9期913-918,978,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：邯郸市科学技术研究与发展计划项目(1823108145)。

摘　　要：目的探讨芹菜素对脓毒症大鼠急性肺损伤的保护作用及可能作用机制。方法将180只实验用SD大鼠按随机数字表法分为6组各30只,假手术组和模型组给予0.9%氯化钠溶液腹腔注射,芹菜素低、中、高剂量预处理组分别给予10 mg/(kg·d)、20 mg/(kg·d)、40 mg/(kg·d)芹菜素腹腔注射,地塞米松预处理组给予5 mg/(kg·d)地塞米松腹腔注射,均1次/d,连续注射7 d后,采用盲肠结扎穿孔法制备脓毒症大鼠模型(假手术组不结扎和穿孔)。造模手术24 h后,检测肺功能(呼吸频率、肺泡通透指数、动脉血氧分压),计算肺组织湿/干重比,HE染色法行肺组织病理学检查并行损伤评分,检测肺组织中内毒素(LPS)、炎症因子指标[肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)]、氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、总抗氧化能力(T-AOC)]水平,Western bolt法检测肺组织中磷酸化核因子-κB(p-NF-κB)表达水平。结果模型组大鼠呼吸频率、肺泡通透指数、肺组织湿/干重比、肺组织病理损伤评分和LPS、TNF-α、IL-1β、IL-6、MDA水平及p-NF-κB蛋白表达量均明显高于假手术组(P均<0.05),动脉血氧分压及肺组织中SOD、CAT、T-AOC活性均明显低于假手术组(P均<0.05);芹菜素中、高剂量预处理组和地塞米松预处理组呼吸频率、肺泡通透指数、肺组织湿/干重比、肺组织病理损伤评分和LPS、TNF-α、IL-1β、IL-6、MDA水平及p-NF-κB蛋白表达量均明显低于模型组(P均<0.05),动脉血氧分压及肺组织中SOD、CAT、T-AOC活性均明显高于模型组(P均<0.05);芹菜素高剂量预处理组上述各指标改善情况均优于地塞米松预处理组(P均<0.05)。结论芹菜素预处理可抑制脓毒症大鼠急性肺损伤,保护肺功能,可能与其抑制炎症反应、氧化应激及NF-κB信号通路有关。Objective It is to investigate the protective effect of apigenin(APG)pretreatment on the acute lung injury in septic rats and its possible mechanism.Methods 180 experimental SD rats were divided into 6 groups with 30 rats according to the random number table method.The sham operation group and the model group were given 0.9%sodium chloride solution by intraperitoneal injection,and the apigenin low,medium and high dose pretreatment groups were respectively given 10 mg/(kg·d),20 mg/(kg·d),40 mg/(kg·d)APG by intraperitoneal injection,the dexamethasone pretreatment group was given 5 mg/(kg·d)dexamethasone by intraperitoneal injection,all 1 times/d.After continuous injection for 7 days,the rat model of sepsis was prepared by cecal ligation and perforation(the sham operation group was not ligated or perforated).In 24 hours after the modeling operation,lung function(respiratory rate,alveolar permeability index,arterial blood oxygen partial pressure)was measured,lung tissue wet-weight/dry-weight ratio was calculated,lung histopathological examination was performed by HE staining method and damage score were evaluated,and the levels of endotoxin(LPS),inflammatory factor index[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)],oxidative stress index[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),total antioxidant capacity(T-AOC)]in lung tissue were detected,the expression levels of phosphorylated nuclear factor-κB(p-NF-κB)was detected by Western bolt method.Results The respiratory frequency,alveolar permeability index,lung tissue wet/dry weight ratio,lung tissue pathological damage score and the levels of LPS,TNF-α,IL-1β,IL-6,MDA and p-NF-κB protein expression in the model group was significantly higher than those in the sham operation group(all P<0.05),and the arterial blood oxygen partial pressure and the activities of SOD,CAT and T-AOC in the lung tissue were significantly lower than those in the sham operation group(all P<0.05).The respiratory rate,alveolar permeability

关 键 词：芹菜素 脓毒症 急性肺损伤 肺功能 氧化应激 炎症反应 

分 类 号：R-332[医药卫生]