犀角地黄汤加味通过NF-κB信号通路对败血症导致的炎症和肺损伤的影响
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摘要
目的研究犀角地黄汤加味对败血症导致的炎症和肺损伤的影响,探讨其对核转录因子-κB(NF-κB)信号通路的调控作用。方法制备败血症小鼠模型,测量血清中乳酸脱氢酶(LDH)反映败血症小鼠的器官损伤程度;HE染色观察败血症小鼠肺组织病理学变化;酶联免疫吸附法测定肺组织中细胞因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、小鼠巨噬细胞炎症蛋白-2(MIP-2)水平;免疫组化法检测肺组织中粒细胞分化抗原-1(Gr-1)的阳性表达;TUNEL法分析败血症小鼠肺中的TUNEL阳性细胞数量;Western blotting法检测肺组织中NF-κB p65蛋白表达。结果犀角地黄汤加味减轻了败血症小鼠的炎症反应和肺损伤程度,以及嗜中性粒细胞浸润。犀角地黄汤加味显著减少了败血症小鼠肺中的TUNEL阳性细胞数量。结论犀角地黄汤加味可以减轻败血症导致的炎症和肺损伤,可能是通过抑制NF-κB信号通路发挥作用。
Objective To investigate the effect of Xijiao Dihuang Decoction on inflammation and lung injury caused by sepsis in children and explore its regulatory effect on NF-κB signaling pathway. Methods The mice model with pediatric sepsis was establishen. Lactate dehydrogenase was used to detect organ damage and inflammation in sepsis mice. HE staining was used to observe the pathological changes of lung tissue in sepsis mice. Interleukin-6(IL-6), Interleukin-1β(IL-1β), and MIP-2 content were measured by enzyme-linked immunosorbent assay. The expression of Gr-1 in lung tissues was determinated by immunohistochemistry. the number of TUNEL-positive cells in the lungs of sepsis mice was analyzed by TUNEL method; Western blotting was used to detect the expression of NF-κB p65 in lung tissue. Results The addition of Xijiao Dihuang Decoction reduced inflammation and lung injury, as well as neutrophil infiltration in septicemic mice. In addition, Xijiao Dihuang Decoction significantly reduced TUNEL-positive cells. Conclusion Xijiao Dihuang Decoction can reduce inflammation and lung injury caused by sepsis in children by inhibiting NF-κB signaling pathway.
Objective To investigate the effect of Xijiao Dihuang Decoction on inflammation and lung injury caused by sepsis in children and explore its regulatory effect on NF-κB signaling pathway. Methods The mice model with pediatric sepsis was establishen. Lactate dehydrogenase was used to detect organ damage and inflammation in sepsis mice. HE staining was used to observe the pathological changes of lung tissue in sepsis mice. Interleukin-6(IL-6), Interleukin-1β(IL-1β), and MIP-2 content were measured by enzyme-linked immunosorbent assay. The expression of Gr-1 in lung tissues was determinated by immunohistochemistry. the number of TUNEL-positive cells in the lungs of sepsis mice was analyzed by TUNEL method; Western blotting was used to detect the expression of NF-κB p65 in lung tissue. Results The addition of Xijiao Dihuang Decoction reduced inflammation and lung injury, as well as neutrophil infiltration in septicemic mice. In addition, Xijiao Dihuang Decoction significantly reduced TUNEL-positive cells. Conclusion Xijiao Dihuang Decoction can reduce inflammation and lung injury caused by sepsis in children by inhibiting NF-κB signaling pathway.
引文
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[14]陈亚利,欧阳军,孟晶茜,等.姜黄素对高尿酸血症大鼠肾组织中TGF-β1、NF-κB表达的影响[J].郑州大学学报:医学版,2018,53(3):360-364.
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[17]陈伟,马磊,杨立山.甘草次酸对哮喘大鼠的抗氧化应激作用及NF-κB信号通路的调控[J].郑州大学学报:医学版,2016,51(6):762-765.
[18]王红,李珊.早发型与晚发型新生儿败血症临床比较[J].郑州大学学报:医学版,2015,50(2):283.
[19]Lawrence T,Fong C.The resolution of inflammation:anti-inflammatory roles for NF-kappaB[J].Int J Biochem Cell Biol,2010,42(4):519-523.
[20]王金磊,李承德,孙宏伟,等.黄芪多糖抑制NF-κB/MAPK信号通路和改善哮喘大鼠气道炎症的作用[J].中国药理学通报,2016,32(4):489-493.
[2]赵凤霞,刘光辉,张健.IL-6和IL-8在诊断新生儿败血症中的价值研究[J].中国当代儿科杂志,2015,17(12):1311-1315.
[3]Lim J C,Golden J M,Ford H R.Pathogenesis of neonatal necrotizing enterocolitis[J].Pediatr Surg Int,2015,31(6):509-518.
[4]Verani J R,Mc Gee L,Schrag S J.Division of Bacterial Dis-eases,National Center for Immunization and Respiratory Diseases.Prevention of perinatal group Bstreptococcal dis-ease-revised guidelines from CDC,2010[J].MMWR Recomm Rep,2010,59(10):1-36.
[5]李建杰.犀角地黄汤临床应用体会[J].中国中医药信息杂志,2012,19(9):89-90.
[6]王立燕,徐若男,韩根成,等.实验性败血症小鼠模型的建立及评价[J].中国实验血液学杂志,2010,18(3):766-770.
[7]刘明月,郭琳瑛,张琪,等小儿真菌性败血症的临床特征和危险因素分析[J].北京医学,2018,40(2):124-126.
[8]崔雪平.124例新生儿败血症的临床特点和病原学分析[J].蚌埠医学院学报,2018,271(7):53-57.
[9]倪倩,徐丁,崔毅.核因子-κB对新生儿败血症的早期诊断价值[J].实用儿科临床杂志,2005,20(12):1221-1222.
[10]潘凤,史源,李华强,等.新生鼠败血症脾脏核因子-κB P65表达[J].实用儿科临床杂志,2003,41(6):426-427.
[11]Sivanandan S,Soraisham A S,Swarnam K.Choice and dura-tion of antimicrobial therapy for neonatal sepsis and meningitis[J].Int J Pediatr,2011,doi:10.1155/2011/712150.
[12]潘凤,史源,李华强,等.新生鼠败血症时核因子-κB的表达[J].中华儿科杂志,2003,41(8):26-29.
[13]周亚妮,李可,刘丹.基于CLP败血症小鼠中补体C5a与白细胞介素-6相关性研究[J].蚌埠医学院学报,2017,42(2):148-150.
[14]陈亚利,欧阳军,孟晶茜,等.姜黄素对高尿酸血症大鼠肾组织中TGF-β1、NF-κB表达的影响[J].郑州大学学报:医学版,2018,53(3):360-364.
[15]Wynn J L,Scumpia P O,Winfield R D,et al.Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists[J].Blood,2008,112(5):1750-1758.
[16]徐家新,赵武,诸宏伟,等.NICU中新生儿败血症及呼吸机相关肺炎的病原菌及耐药性分析[J].蚌埠医学院学报,2016,41(2):164-167.
[17]陈伟,马磊,杨立山.甘草次酸对哮喘大鼠的抗氧化应激作用及NF-κB信号通路的调控[J].郑州大学学报:医学版,2016,51(6):762-765.
[18]王红,李珊.早发型与晚发型新生儿败血症临床比较[J].郑州大学学报:医学版,2015,50(2):283.
[19]Lawrence T,Fong C.The resolution of inflammation:anti-inflammatory roles for NF-kappaB[J].Int J Biochem Cell Biol,2010,42(4):519-523.
[20]王金磊,李承德,孙宏伟,等.黄芪多糖抑制NF-κB/MAPK信号通路和改善哮喘大鼠气道炎症的作用[J].中国药理学通报,2016,32(4):489-493.