雾化吸入和腹腔注射依达拉奉对烟雾吸入性损伤肺模型大鼠保护作用的比较研究
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篇名: 雾化吸入和腹腔注射依达拉奉对烟雾吸入性损伤肺模型大鼠保护作用的比较研究
TITLE: Comparative Study of Protective Effects of Atomization Inhalation and Intraperitoneal Injection of Edaravone on Smoke Inhalation Lung Injury Model Rats
摘要: 目的:比较雾化吸入和腹腔注射依达拉奉对烟雾吸入性肺损伤模型大鼠急性肺损伤的保护作用。方法:将30只雄性SD大鼠按照随机数字表法分为正常对照组(A组)、致伤空白组(B组)、致伤腹腔注射治疗组(C组)和致伤低、高剂量雾化吸入治疗组(D、E组),每组6只。B~E组大鼠均被置于含松木屑的烟雾发生器中复制烟雾吸入性肺损伤模型;A组大鼠除不放松木屑外,其余操作同上。造模后30min,C组大鼠腹腔注射依达拉奉18mg/kg(每间隔70min重复1次,共4次);D、E组大鼠雾化吸入依达拉奉9、18mg/kg(雾化吸入10min,每间隔60min重复1次,共4次);A、B组大鼠不作任何处理。末次给药后6h,进行大鼠动脉血气分析,并计算大鼠肺湿干比(W/D)和肺组织含水率;采用双抗体夹心酶联免疫吸附测定(ELISA)法检测其血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-10含量;采用ELISA等方法检测其肺组织中丙二醛(MDA)、髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、胱天蛋白酶3(Caspase-3)含量;采用苏木精-伊红染色法观察其肺组织病理改变;采用TUNEL法检测其肺组织细胞凋亡率。结果:A组大鼠肺组织未见异常;B组大鼠肺组织中可见出血及水肿,肺泡结构难以辨认,并可见炎症细胞和红细胞浸润;C~E组大鼠肺组织上述症状均有不同程度改善。与A组比较,其余组大鼠动脉氧分后和吸入氧浓度比值(PaO2/FiO2)以及肺组织SOD含量均显著降低(P<0.05);肺含水率、W/D,血清TNF-α、IL-6、IL-10含量以及肺组织MDA、MPO、Caspase-3含量和细胞凋亡率均显著升高(P<0.05)。与B组比较,各给药组大鼠动脉PaO2/FiO2以及血清IL-10含量均显著升高(P<0.05);肺含水率、W/D,血清TNF-α、IL-6含量以及肺组织MDA、MPO、Caspase-3含量和细胞凋亡率均显著降低,且呈剂量依赖性(P<0.05)。结论:依达拉奉对烟雾吸入性肺损伤模型大鼠具有一定的保护作用,可剂量依赖性地减少炎症介质和(或)细胞因子的产生及释放、减轻过氧化损伤并抑制细胞凋亡,且雾化吸入较腹腔注射的效果更明显。
ABSTRACT: OBJECTIVE:To compare the protective effect of atomization inhalation and intraperitoneal injection of edaravone on acute lung injury in smoke inhalation lung injury model rats. METHODS :Thirty male SD rats were divided into normal control group(group A ),injury group (group B ),intraperitoneal injection group (group C ),low-dose aerosol inhalation group (group D),high-dose aerosol inhalation group (group E )according to random numble table ,with 6 rats in each group. Group B-E were placed in smoke generator containing pine sawdust to induce smoke inhalation lung injury model. In group A ,the operation was the same as above except that the pine sawdust was not placed. Thirty minutes after modeling ,group C were injected intraperitoneally with edaravone 18 mg/kg(every 70 min,4 times in total ). Group D and E inhaled edaravone 9,1.8 mg/kg(every 60 min,lasting for 10 min each time ,4 times in total ). The rats were treated by no means in group A and group B. Six hours after last medication,arterial blood gas analysis was performed ,and the lung wet to dry ratio (W/D)and water content of lung tissue were calculated. The levels of TNF-α,IL-6 and IL- 10 in serum were detected by double antibody ELISA. The contents of MDA ,MPO, SOD and Caspase- 3 in lung tissue were determined by ELISA and other methods. HE staining was used to observe the pathological changes of lung tissue. The apoptotic rate of cells in lung tissue were determined by TUNEL assay. RESULTS :No abnormality was found in lung tissue of group A ;in group B ,hemorrhage and edema were found in lung tissue ,alveolar structure was difficult to identify,and inflammatory cells and red blood cell infiltration were seen. Above symptoms of rats in group C-E were improved to different extent. Compared with group A ,PaO2/FiO2 and SOD content of lung tissue were decreased significantly in other groups (P<0.05);water content of lung tissue ,W/D,serum contents of TNF-α,IL-6 and IL- 10,the contents of MDA ,MPO and Caspase-3 in lung tissue ,apoptotic rate were increased significantly (P<0.05). Compared with group B ,PaO2/FiO2 and serum contents of IL- 10 were increased significantly in administration groups (P<0.05);water content of lung tissue ,W/D,serum contents of TNF-α and IL-6,the contents of MDA ,MPO and Caspase- 3 in lung tissue ,apoptotic rate were significantly decreased,in dose-dependent manner (P<0.05). CONCLUSIONS :Edaravone has a certain protective effect on smoke inhalation lung injury model rat. It can reduce the production and release of inflammatory mediators and/or cytokines ,reduce the peroxide damage and inhibit cell apoptosis in a dose-dependent manner. The effect of atomization inhalation is more obvious than that of intraperitoneal injection.
期刊: 2021年第32卷第01期
作者: 肖长栓,刘娅平,杨景哲
AUTHORS: XIAO Changshuan,LIU Yaping,YANG Jingzhe
关键字: 雾化吸入;腹腔注射;依达拉奉;吸入性肺损伤;量效关系;大鼠;保护作用;炎症因子
KEYWORDS: Atomization inhalation ; Intraperitoneal injection ; Edaravone; Smoke inhalation lung injury ; Dose-effect
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