基于NF-κB信号通路的中药治疗脓毒症研究进展
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摘要
脓毒症是由感染、手术、创伤等引起的全身炎症反应综合征(SIRS),死亡率高、治疗费用高、医疗资源消耗大,给医疗行业甚至是国家经济都带来了很大的负担,因此,找到治疗脓毒症的有效措施刻不容缓。目前针对脓毒症的发病机制,使用了一定的药物治疗,抗生素、糖皮质激素、血管活性药物等,但其治疗效果并不理想,副作用多,预后效果差,临床死亡率依然居高不下。中医讲究整体观念,辨证论治,对于脓毒症的治疗具有功效独特、副作用相对较小等优势,吸引了无数来自世界各地有志于解决脓毒症的科研及临床工作者们的目光。近年来,一些中药复方、中成药、单味中药及活性成分越来越多的作为新型药物用于预防、治疗脓毒症,并且得到了广泛的认可,在一定程度上降低了脓毒症患者的死亡率、炎性指标等,对于脓毒症的治疗起到了重要的作用。本文就核转录因子-κB(NF-κB)信号通路在脓毒症中的作用及以NF-κB信号通路相关蛋白为作用靶点的中药治疗脓毒症的研究进展进行综述。
Sepsis is a kind of systemic inflammatroy response syndrome( SIRS) induced by severe infection,operation,and trauma,with high mortality rate,treatment cost,and high consumption of medical resources. It has caused a great burden to the medical industry and even the national economy. Therefore,it is urgent to find effective treatment methods for sepsis. At present,the sepsis has been treated with certain drugs pointing at its pathogenesis,such as antibiotics,glucocorticoids,and vasoactive drugs.,but the therapeutic effect is not ideal,with many side effects,poor prognosis,and high clinical mortality. Based on the overall macrodialectical thinking mode,and with the unique effect and low side effect,traditional Chinese medicine( TCM) has attracted the attention from researchers and clinicians around the world for treatment of sepsis. In recent years,some traditional Chinese medicine prescriptions,Chinese patent medicines,single Chinese medicines and active ingredients are increasingly used as new drugs to prevent and treat sepsis. Such treatment methods have been widely recognized and have reduced the mortality and inflammatory indexes of patients to a certain extent,playing an important role in the prevention and treatment of sepsis. In this paper,the actions of nuclear factor kappa B( NF-κB) signal pathway in sepsis as well as the advances in research of NF-κB signal pathway-related proteins in Chinese medicine for sepsis were reviewed.
Sepsis is a kind of systemic inflammatroy response syndrome( SIRS) induced by severe infection,operation,and trauma,with high mortality rate,treatment cost,and high consumption of medical resources. It has caused a great burden to the medical industry and even the national economy. Therefore,it is urgent to find effective treatment methods for sepsis. At present,the sepsis has been treated with certain drugs pointing at its pathogenesis,such as antibiotics,glucocorticoids,and vasoactive drugs.,but the therapeutic effect is not ideal,with many side effects,poor prognosis,and high clinical mortality. Based on the overall macrodialectical thinking mode,and with the unique effect and low side effect,traditional Chinese medicine( TCM) has attracted the attention from researchers and clinicians around the world for treatment of sepsis. In recent years,some traditional Chinese medicine prescriptions,Chinese patent medicines,single Chinese medicines and active ingredients are increasingly used as new drugs to prevent and treat sepsis. Such treatment methods have been widely recognized and have reduced the mortality and inflammatory indexes of patients to a certain extent,playing an important role in the prevention and treatment of sepsis. In this paper,the actions of nuclear factor kappa B( NF-κB) signal pathway in sepsis as well as the advances in research of NF-κB signal pathway-related proteins in Chinese medicine for sepsis were reviewed.
引文
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[2]Mayr F B,Yende S,Angus D C.Epidemiology of severe sepsis[J].Virulence,2014,5(1):4-11.
[3]Lopez-Bushnell K,Demaray W S,Jaco C.Reducing Sepsis Motality[J].Medsurg Nurs,2014,23(1):9-14.
[4]刘毅,宋诗铎,王洪霞.ICU医院感染相关脓毒症病原菌分布及耐药性分析[J].中华医院感染学杂志,2010,20(3):421-423.
[5]赵国桢,郭玉红,李博,等.中医药防治脓毒症的研究进展[J].中国中药杂志,2017,42(8):1423-1429.
[6]刘清泉,张伟,姜良铎.瘀毒伤络、阻络病机与脓毒症[J].中国中医药现代远程教育,2010,17(8):199-200.
[7]王鹏程,赵珊,冯健,等.基于NF-κB信号通路的中药抗溃疡性结肠炎研究进展[J].中草药2015,46(10):1556-1561.
[8]周霞,凌斌,孙洁,等.HMGB1-RAGE/TLRs-NF-κB信号通路与脓毒症关系的研究进展[J].山东医药,2016,56(37):101-103.
[9]王晶晶,杨敬平,齐明禄.TLR4介导的信号通路与脓毒症相关性研究[J].临床肺科杂志,2015,20(4):725-727.
[10]LIU F,FU Y,WEI C,et al.The expression of GPR109A,NF-κB and IL-1βin peripheral blood leukocytes from patients with type 2 diabetes[J].Ann Clin Lab Sci,2014,44(4):443-448.
[11]冯玉玺,李爱丽,徐建欣.“三证三法”治疗脓毒症心肌抑制的研究进展[J].医学综述,2013,19(15):2775-2777.
[12]王非,骆仙芳,赵玮,等.清瘟败毒饮影响急性肺损伤大鼠肺组织NF-κB p65表达的实验研究[J].中华中医药学刊,2011,29(6):1290-1295.
[13]王国全,李莎,余林中,等.基于JAK2/STAT3和IKKα/NF-κB信号通路探讨清瘟败毒饮对脓毒症急性肺损伤大鼠的保护作用及机制研究[J].中药药理与临床,2018,34(3):2-5.
[14]李翀,翁书和,梁莉萍,等.黄连解毒汤对脓毒症模型小鼠肺损伤的保护作用及其机制研究[J].江苏中医药,2018,50(3):79-82.
[15]罗鹏.大承气汤对多器官功能障碍综合征大鼠小肠平滑肌线粒体凋亡途径和NF-κB、COX-2蛋白表达影响[D].大连:大连医科大学,2014.
[16]杨胜兰,金阳,沈霖,等.大承气汤含药血清对内毒素刺激的人支气管上皮细胞表达CVA-1、e NOs和NF-κB的影响[J].中国中西医结合杂志,2012,32(8):1088-1094.
[17]李淑芳,汪海慧,闫国良.抗炎合剂对脓毒症急性肺损伤TLR4/My D88信号通路的干预研究[J].上海中医药杂志,2017,51(3):177-180.
[18]张祎.大黄基于TLR4-MAPK-NF-κB炎症信号通路治疗内毒素血症的相关分子机制研究[D].成都:成都中医药大学,2015.
[19]MENG G,LIU Y,LOU C.Emodin suppresses lipopolysaccharid-induced pro-inflammatory responses and NF-κB activation by disrupting lipid rafts in CD14-negative endothelial cell[J].Br J Pharmacol,2010,161(7):1628-1644.
[20]奚百顺,黄培志,童朝阳,等.核因子κB在黄芩苷对脓毒症大鼠肾脏保护中的作用[J].中国临床医学,2011,18(4):469-472.
[21]胡静,马琳,张坚,等.连翘的研究进展[J].中南药学,2012,10(10):760-764.
[22]曾小燕.连翘酯苷A通过HMGB1/TLR4/NF-κB信号通路抗内毒素的实验研究[D].南昌:南昌大学,2016.
[23]潘晓龙.连翘苷对LPS诱导炎症反应的影响及分子机制的研究[D].南京:南京师范大学,2014.
[24]张毅.连翘对内毒素作用下大鼠脾脏淋巴细胞TLR4、NF-κB、IL-6、IL-10的影响[D].太原:山西医科大学,2014.
[25]李杨,周福军,单淇,等.中药有效成分治疗脓毒症的研究进展[J].现代药物与临床,2013,28(2):242-246.
[26]SHI Q,CAO J,FANG L,et al.Geniposide suppresses LPS-induced nitric oxide,PGE2and inflammatory cytokine by downregulating NF-κB,MAPK and AP-1signaling pathways in macrophages[J].Int Immunopharmacol,2014,20(2):298-306.
[27]HUANG L,WANG C,NAREN G,et al.Effect of geniposide on LPS-induced activation of TLR4-NF-κB pathway in RAW264.7 macrophage cell line[J].Chin J Cell Mol Imm,2013,29(10):1012-1014.
[28]ZHANG X,SUN C Y,ZHANG Y B,et al.Kegan Liyan oral liquid ameliorates lipopolysaccharide-induced acute lung injury through inhibition of TLR4-mediated NF-κB signaling pathway and MMP-9 expression[J].J Ethnopharmacol,2016,186(20):91-102.
[29]WANG J,HOU J,ZHANG P,et al.Geniposide reduces inflammatory responses of oxygen-glucose deprived rat microglial cells via inhibition of the TLR4 signaling pathway[J].Neurochem Res,2012,37(10):2235-2248.
[30]WANG J,TAN X F,Nguyen V S,et al.A quantitative chemical proteomics approach to profile the specific cellular targets of andrographolide,a promising anticancer agent that suppresses tumor metastasis[J].Mol Cell Proteomics,2014,13(3):876-886.
[31]ZHU T,WANG D X,ZHANG W,et al.Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-kappa B[J].PLo S One,2013,8(2):e56407.
[32]杨新娟.穿心莲内酯对脓毒血症大鼠肝损伤的保护作用[J].中成药,2015,37(10):2296-2298.
[33]贺胜男.穿心莲内酯对LPS诱导的炎性反应的抗炎作用及其机制研究[D].合肥:安徽农业大学,2017.
[34]朱涛.穿心莲内酯通过抑制NF-κB信号通路对LPS诱导的小鼠ALI/ARDS的保护机制的实验研究[D].重庆:重庆医科大学,2013.
[35]肖蓉.中药方“蒲和饮”对小鼠的抗炎效果及抗炎机制研究[D].重庆:西南大学,2014.
[36]CHANG J,SHEN Y C,WANG Y H,et al.Honokiol protects rats against eccentric exercise-induced skeletal muscle damage by inhibiting NF-kappa B induced oxidative stress and inflammation[J].Eur J Pharmacol,2009,610(3):119-127.
[37]Kim B H,Cho J Y.Anti-inflammatory effect of honokiol is mediated by P13K/Akt pathway suppression[J].Acta Pharmacol Sin,2008,29(1):113-122.
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