黔产毛蒟挥发油对油酸致大鼠急性肺损伤的影响及其机制
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摘要
为研究黔产毛蒟挥发油在油酸诱导的大鼠急性肺损伤中的作用及其机制。实验将雄性成年清洁级SD大鼠按照体重随机分为对照组、油酸模型组和毛蒟挥发油组(0.125、0.25、0.5 mL/kg)。油酸模型组大鼠采用右侧颈静脉注射油酸0.2 mL/kg形成急性肺损伤模型;毛蒟挥发油组大鼠在油酸造模前30分钟静脉注射毛蒟挥发油;建模4 h后处死,留取标本。观察各组肺组织病理学形态并进行肺损伤评分,同时测定血气分析值、右下肺湿干重、肺通透指数以及肺泡灌洗液中TNF-α、IL-6和IL-1β炎症因子的含量,最后采用免疫组化和Western Blot检测p38MAPK和p-p38MAPK蛋白的表达量。结果表明大鼠PaO_2和PaO_2/FiO_2在油酸模型组明显低于对照组,同时右下肺湿干重、肺通透指数以及肺泡灌洗液中TNF-α、IL-6和IL-1β炎症因子的含量在油酸模型组明显高于对照组。油酸模型组肺组织病理学显示肺损伤明显;毛蒟挥发油组上述指标较油酸模型组明显减轻。p-p38MAPK蛋白表达量在油酸模型组中明显高于对照组,而p-p38MAPK蛋白表达量在毛蒟挥发油组中明显低于油酸模型组。实验证明黔产毛蒟挥发油能够通过抑制p38MAPK通路减少急性肺损伤炎症因子的产生,对急性肺损伤具有较好的保护作用。
To investigate the influence of volatile oil of Piper puberulum from Guizhou in oleic acid-induced acute lung injury and its mechanism.Healthy adult male SD rats were randomly divided into three equal groups:normal control group,oleic acid model group and volatile oil group(0.125 mL/kg,0.25 mL/kg and 0.5 mL/kg).Oleic acid model group was administered oleic acid(0.2 mL/kg) via right jugular vein;In volatile oil group,volatile oil group was injected via jugular vein,followed 30 min before by oleic acid infusion;At the 4 hours animals were sacrificed,pathological changes of the lung tissue were examined with light microscope.Arterial blood gas,the wet/dry weight(W/D) of the right lower lung were examined,lung index,LPI and Levels of TNF-α,IL-6 and IL-1β in BALF were examined.The expression conditions of p38 MAPK and p-p38 MAPK were determined by Western blot and immunohistochemical method.The results show that compared to control group,PaO2 and PaO2/FiO2 declined in the animals of oleic acid model group,while right lower lung wet/dry ratio,lung index,LPI and Levels of TNF-α,IL-6 and IL-1β in BALF were increased obviously.Pulmonary edema was observed in injured lung pathology.Compared to oleic acid model group,those indexes were improved in volatile oil group.The lung tissue levels of p-p38 MAPK expressions were markedly higher in oleic acid model group compared to control group.Compared to oleic acid model group,the expression of p-p38 MAPK was reduced in volatile oil group.Experiments have proved that volatile oil of Piper puberulum from Guizhou has a better protection effect to acute lung injury and reduces the cytokine production and it can exert its action by inhibiting p38 MAPK pathway.
To investigate the influence of volatile oil of Piper puberulum from Guizhou in oleic acid-induced acute lung injury and its mechanism.Healthy adult male SD rats were randomly divided into three equal groups:normal control group,oleic acid model group and volatile oil group(0.125 mL/kg,0.25 mL/kg and 0.5 mL/kg).Oleic acid model group was administered oleic acid(0.2 mL/kg) via right jugular vein;In volatile oil group,volatile oil group was injected via jugular vein,followed 30 min before by oleic acid infusion;At the 4 hours animals were sacrificed,pathological changes of the lung tissue were examined with light microscope.Arterial blood gas,the wet/dry weight(W/D) of the right lower lung were examined,lung index,LPI and Levels of TNF-α,IL-6 and IL-1β in BALF were examined.The expression conditions of p38 MAPK and p-p38 MAPK were determined by Western blot and immunohistochemical method.The results show that compared to control group,PaO2 and PaO2/FiO2 declined in the animals of oleic acid model group,while right lower lung wet/dry ratio,lung index,LPI and Levels of TNF-α,IL-6 and IL-1β in BALF were increased obviously.Pulmonary edema was observed in injured lung pathology.Compared to oleic acid model group,those indexes were improved in volatile oil group.The lung tissue levels of p-p38 MAPK expressions were markedly higher in oleic acid model group compared to control group.Compared to oleic acid model group,the expression of p-p38 MAPK was reduced in volatile oil group.Experiments have proved that volatile oil of Piper puberulum from Guizhou has a better protection effect to acute lung injury and reduces the cytokine production and it can exert its action by inhibiting p38 MAPK pathway.
引文
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17 Li QC,Liang Y,Tian Y,et al.Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway[J].J Buon,2016,21(1):87-94.
2 Qin Q,Que JH,Zhang YQ,et al.pharmacodynamics study on the anti-rheumatoid effect of n-butanol extract of sepidium japonicum[J].Asia-Pacific Trad Me (亚太传统医药),2015,11(4):13-15.
3 Millar FR,Summers C,Griffiths MJ,et al.The pulmonary endothelium in acute respiratory distress syndrome:insights and therapeutic opportunities[J].Thorax,2016,71:462-473.
4 Zhang X,Wu W,Zhu Y,et al.Abdominal muscle activity during mechanical ventilation increases lung injury in severe acute respiratory distress syndrome[J].PLoS One,2016,11:e145694
5 Kao SJ,Yeh DY,Chen HI.Clinical and pathological features of fat embolism with acute respiratory distress syndrome[J].Clin Sci(Lond),2007,113:279-285.
6 Wang G,Han D,Zhang Y,et al.A novel hypothesis:Up-regulation of HO-1 by activation of PPAR-gamma inhibits HMGB1-RAGE signaling pathway and ameliorates the development of ALI/ARDS[J].J Thorac Dis,2013,5:706-710.
7 Vadasz I,Morty RE,Kohstall MG,et al.Oleic acid inhibits alveolar fluid reabsorption:A role in acute respiratory distress syndrome[J].Am J Respir Crit Care Med,2005,171:469-479.
8 Ito K,Mizutani A,Kira S,et al.Effect of Ulinastatin,a human urinary trypsin inhibitor,on the oleic acid-induced acute lung injury in rats via the inhibition of activated leukocytes[J].Injury,2005,36:387-394.
9 Shen W,Gan J,Xu S,et al.Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement of NF-κB pathway[J].Pharmacol Res,2009,60:296-302.
10 Sun Y,Yang R,Zhong JG,et al.Aerosolised surfactant generated by a novel noninvasive apparatus reduced acute lung injury in rats[J].Crit Care,2009,13(2):31.
11 He X,Han B,Mura M,et al.Angiotensin-converting enzyme inhibitor captopril prevents oleic acid-induced severe acute lung injury in rats[J].Shock,2007,28:106-111.
12 Liu KX,Wu WK,He W,et al.Ginkgo biloba extract(EGb 761) attenuates lung injury induced by intestinal ischemia/reperfusion in rats:roles of oxidative stress and nitric oxide[J].World J Gastroenterol,2007,13:299-305.
13 Guo J,Li M,Yang Y,et al.Protective effect of chlorogenic acid on acute lung injury in mice[J].Nat Prod Res Dev(天然产物研究与开发),2018,30:1214-1218.
14 Bai X,Fan L,He T,et al.SIRT1 protects rat lung tissue against severe burn-induced remote ALI by attenuating the apoptosis of PMVECs via p38 MAPK signaling[J].Sci Rep,2015,5:10277.
15 Akrami H,Mahmoodi F,Havasi S,et al.PlGF knockdown inhibited tumor survival and migration in gastric cancer cell via PI3K/Akt and p38MAPK pathways[J].Cell Biochem Funct,2016,34:173-180.
16 Liu S,Feng G,Wang GL,et al.p38MAPK inhibition attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway[J].Eur J Pharmacol,2008,584:159-165.
17 Li QC,Liang Y,Tian Y,et al.Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway[J].J Buon,2016,21(1):87-94.