麦角甾醇对LPS诱导的肺损伤小鼠的抗炎作用研究
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摘要
目的研究麦角甾醇对LPS诱导的小鼠急性肺损伤的抗炎作用研究。方法取50只雄性BABL/c小鼠随机分为5组:空白对照组、模型组、地塞米松组(2 mg/kg)、麦角甾醇低剂量组(20 mg/kg)、麦角甾醇高剂量组(40 mg/kg)。空白对照组和模型组按体积给予生理盐水,地塞米松组(2 mg/kg)、麦角甾醇组(20、40mg/kg)灌胃给予相应药物。给药1 h后,除空白对照组,其余各组小鼠气管滴注20μg LPS。检测小鼠肺干湿重比(W/D),肺泡灌洗液(BALF)中超氧化物歧化酶(SOD)水平、丙二醛(MDA)含量,血清与肺泡灌洗液炎性细胞因子(TNF-α、IL-1β、IL-6)水平。取各组小鼠肺组织做HE染色,并检测肺组织Rho、ROCK1、ROCK2、p-NF-κBP65、NF-κBP65、p-IκBα、IκBα蛋白表达。结果麦角甾醇20、40 mg/kg能显著提升LPS诱导的急性肺损伤小鼠血清SOD水平,降低MDA含量;改善血清及肺泡灌洗液炎症因子水平和肺组织病理学改变;降低肺组织Rho、ROCK1、ROCK2、p-NF-κBP65、p-IκBα蛋白表达。结论麦角甾醇对LPS诱导的急性肺损伤小鼠有保护作用,其作用可能与Rho/ROCK/NF-κB信号通路有关。
Objective To investigate the anti-inflammatory effect of ergosterin on lipopolysaccharide( LPS)-induced acute lung injury( ALI). Methods Totally 50 BABL/c mice were divided into 5 groups randomly : control group,model group,dexamethasone group( 2 mg/kg),ergosterin( 20 mg/kg),ergosterin( 40 mg/kg). The mice were given ergosterin or dexamethasone at 1 h before intratracheal instillation of LPS. The lung wet-to-dry weight( W/D)ratio,the level of super oxide dismutase( SOD) and the content of malondialdehyde( MDA) in bronchoalveolar lavage fluid( BALF),and the levels of tumor necrosis factor-α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) in BALF were detected. The protein expression of Rho,ROCK1,ROCK2,p-NF-κBP65,NF-κBP65,p-IκBα and IκBα in lung tissue was analyzed. Results Ergosterin of 20 mg/kg and 40 mg/kg could increase the level of SOD and decrease the content of MDA,and improve the levels of pro-inflammatory cytokines in serum and BALF and pathological changes. It could also decrease the protein expression of Rho,ROCK1,ROCK2,p-NF-κBP65 and p-IκBα in lung tissue. Conclusion Ergosterin can ameliorate the LPS-induced acute lung injury in mice and its related mechanism might be related to inhibition of Rho/ROCK/NF-κB pathway.
Objective To investigate the anti-inflammatory effect of ergosterin on lipopolysaccharide( LPS)-induced acute lung injury( ALI). Methods Totally 50 BABL/c mice were divided into 5 groups randomly : control group,model group,dexamethasone group( 2 mg/kg),ergosterin( 20 mg/kg),ergosterin( 40 mg/kg). The mice were given ergosterin or dexamethasone at 1 h before intratracheal instillation of LPS. The lung wet-to-dry weight( W/D)ratio,the level of super oxide dismutase( SOD) and the content of malondialdehyde( MDA) in bronchoalveolar lavage fluid( BALF),and the levels of tumor necrosis factor-α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) in BALF were detected. The protein expression of Rho,ROCK1,ROCK2,p-NF-κBP65,NF-κBP65,p-IκBα and IκBα in lung tissue was analyzed. Results Ergosterin of 20 mg/kg and 40 mg/kg could increase the level of SOD and decrease the content of MDA,and improve the levels of pro-inflammatory cytokines in serum and BALF and pathological changes. It could also decrease the protein expression of Rho,ROCK1,ROCK2,p-NF-κBP65 and p-IκBα in lung tissue. Conclusion Ergosterin can ameliorate the LPS-induced acute lung injury in mice and its related mechanism might be related to inhibition of Rho/ROCK/NF-κB pathway.
引文
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[15]Miyata K,Satou R,Shao W,et al.ROCK/NF-κB axis-dependent augmentation of angiotensinogen by angiotensin II in primary-cultured preglomerular vascular smooth muscle cells[J].Am J Physiol Renal Physiol,2014,306(6):F608-F618.
[2]凌亚豪,魏金锋,王爱平,等.急性肺损伤和急性呼吸窘迫综合征发病机制的研究进展[J].癌变·畸变·突变,2017,29(2):151-154.
[3]李琴,樊佳,陈斌,等.自噬对脂多糖致大鼠急性肺损伤模型的炎症调控[J].中华实用诊断与治疗杂志,2017,31(4):328-331.
[4]杨安伦,陈忠,李建生.响应面设计法优选金蝉花麦角甾醇提取工艺[J].实用药物与临床,2015,18(11):1351-1355.
[5]Zhu L,Chen T,Chang X,et al.Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK/NF-κB pathw ay[J].Neuropharmacology,2016,103:134-142.
[6]Huang Z,Nan C,Wang H,et al.Crocetin ester improves myocardial ischemia via Rho/ROCK/NF-κB pathw ay[J].Int Immunopharmacol,2016,38:186-193.
[7]Tsai SH,Huang PH,Peng YJ,et al.Zoledronate attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of Rho/ROCK-dependent JNK and NF-κB pathw ay[J].Cardiovasc Res,2013,100(3):501-510.
[8]Cooke KR,Yanik G.Acute lung injury after allogeneic stem cell transplantation:is the lung a target of acute graft-versus-host disease[J].Bone Marrow Transplant,2004,34(9):753-765.
[9]Briel M,Meade M,Mercat A,et al.Higher vs lower positive end-expiratory pressure in patients w ith acute lung injury and acute respiratory distress syndrome:systematic review and meta-analysis[J].JAM A,2010,303(9):865-873.
[10]赵利利,戎浩,孙芳云.内毒素致急性肺损伤的发病机制研究进展[J].实用药物与临床,2015,18(4):466-469.
[11]段炼,魏毅涛,刘曼玲,等.中草药对急性肺损伤的保护机制研究进展[J].医学研究生学报,2016,29(5):533-537.
[12]Wu X,Lu Y,Dong Y,et al.The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-α,IL-6,and IL-1β[J].Neurobiol Aging,2012,33(7):1364-1378.
[13]Hung CN,Huang HP,Wang CJ,et al.Sulforaphane inhibits TNF-α-induced adhesion molecule expression through the Rho A/ROCK/NF-κB signaling pathw ay[J].J M ed Food,2014,17(10):1095-1102.
[14]Sun H,Kamanova J,Lara-Tejero M,et al.A family of salmonella type III secretion effector proteins selectively targets the NF-κB signaling pathw ay to preserve host homeostasis[J].PLo S Pathog,2016,12(3):e1005484.
[15]Miyata K,Satou R,Shao W,et al.ROCK/NF-κB axis-dependent augmentation of angiotensinogen by angiotensin II in primary-cultured preglomerular vascular smooth muscle cells[J].Am J Physiol Renal Physiol,2014,306(6):F608-F618.