寇小妮,解新科,郝明霞,吴维,樊晓丹,宋春荣

• 1:陕西中医药大学附属医院

摘要(Abstract)：

目的观察臭牡丹大黄素对小鼠急性肝衰竭的治疗作用及肝细胞内质网应激的影响并探讨其作用机制。方法提取臭牡丹大黄素,将30只雄性C57BL/6小鼠随机均分为对照组、模型组和干预组。干预组在建模前6 h腹腔给予臭牡丹大黄素(80 mg/kg)。模型组和干预组腹腔注射D-氨基半乳糖(700 mg/kg)和脂多糖(10μg/kg),对照组给予等量0.9%氯化钠注射液,6 h后造模成功,对肝组织进行HE染色,检测血清中谷丙转氨酶(ALT)和谷草转氨酶(GOT)水平,El检测肝组织中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、GSK3β、p-GSK3β、ERK、JNK、p38和Caspase-3表达水平及肝组织细胞凋亡情况。结果对照组大鼠肝脏结构正常;模型组出现肝小叶结构紊乱,出血,存在炎性细胞浸润和肝细胞坏死;干预组病理改变较模型组减轻。与对照组比较,模型组ALT、GOT、IL-1β、IL-6、TNF-α、GSK3β、p-GSK3β、ERK、JNK、p38、Caspase-3和细胞凋亡水平显著增高(P <0.05);与模型组比较,干预组ALT、GOT、IL-1β、IL-6、TNF-α、GSK3β、p-GSK3β、ERK、JNK、p38、Caspase-3和细胞凋亡水平显著降低(P<0.05)。结论臭牡丹大黄素可以减轻小鼠ALF的炎症反应,减轻肝细胞坏死和凋亡,发挥治疗作用,其机制可能与通过抑制ERS相关信号分子有关。

关键词(KeyWords)： 急性肝衰竭;臭牡丹大黄素;肝细胞内质网应激;小鼠

Abstract:

Keywords:

基金项目(Foundation): 陕西省科技厅社会发展领域项目（2018SF295）

作者(Author): 寇小妮,解新科,郝明霞,吴维,樊晓丹,宋春荣

参考文献(References)：

• [1]汪增秀，廉亚男，谭善忠，等.扶正化瘀方对慢性肝损伤大鼠慢加急性肝衰竭形成的预防作用[J].中国中医急症，2017,26(8):1333-1335.
• [2] None. EASL Clinical Practical Guidelines on the management of acute(fulminant)liver failure[J]. Journal of Hepatology,2017,66(5):1047-1081.
• [3] Liu Y,Pan X,Li S,et al. Endoplasmic reticulum stress restrains hepatocyte growth factor expression in hepatic stellate cells and rat acute liver failure model[J]. Chemico-Biological Interactions,2017,15(2):156-163.
• [4]谈志丽，钟欢，朱彤，等.糖原合成激酶3β在急性肝衰竭免疫炎症反应中的作用及机制研究进展[J].免疫学杂志，2017,33(6):93-98.
• [5] Meunier CN,Cancela JM,Fossier P. Lack of GSK3βactivation and modulation of synaptic plasticity by dopamine in 5-HT1A-receptor KO mice[J]. Neuropharmacology,2017,113(15):124-136.
• [6] Xian Zhang,Wei Jiang,AiLing Zhou,et al. Inhibitory effect of oxymatrine on hepatocyte apoptosis via TLR4/PI3K/Akt/GSK-3βsignaling pathway[J]. World Journal of Gastroenterology,2017,143(21):93-103.
• [7]徐文明，林建聪，陈美姬，等.糖原合酶激酶-3β与内质网应激相互作用参与高糖引起的人脐静脉内皮细胞损伤[J].南方医科大学学报，2018,38(5):114-121.
• [8]曾丹，刘莉，谭眉灵，等.臭牡丹大黄素对臭氧应激小鼠模型TLR4/MyD88/NF-κB信号通路的调节作用[J].中药新药与临床药理，2018,29(5):53-57.
• [9] Hong X,Xufeng T,Shilin X,et al. Emodin alleviates sodium taurocholate-induced pancreatic acinar cell injury via MicroRNA-30a-5p-Mediated inhibition of high-temperature requirement A/transforming growth factor beta 1 inflammatory signaling[J]. Frontiers in Immunology,2017,8(5):1488-1495.
• [10]杨昊臻，陈珑，童晶晶，等. D-半乳糖胺/脂多糖所致小鼠急性肝衰竭模型正交试验优化研究[J].中华肝脏病杂志，2013,21(6):464-466.
• [11] Subsequently. The protective effect of cordycepin on DGalactosamine/Lipopolysaccharide-Induced acute liver injury[J]. Mediators of Inflammation,2017,17(1):394-406.
• [12] Mosoian A,Zhang L,Hong F,et al. Frontline Science:HIV infection of Kupffer cells results in an amplified proinflammatory response to LPS[J]. Journal of Leukocyte Biology,2017,101(5):1364-1372.
• [13] Rodrigues EM,Rogério Fernandes,Susin R. Immune reconstitution inflammatory syndrome as a cause of autoimmune hepatitis and acute liver failure[J]. Revista Brasileira De Terapia Intensiva,2017,29(3):382-385.
• [14] Liyan C,Feng R,Haiyan Z,et al. Inhibition of glycogen synthase kinase 3βameliorates D-GalN/LPS-Induced liver injury by reducing endoplasmic reticulum stress-triggered apoptosis[J]. PLoS ONE,2012,7(9):5202-5215.
• [15] Chen L,Liu L,Xie ZY,et al. Endoplasmic reticulum stress facilitates the survival and proliferation of nucleus pulposus cells in TNF-αstimulus by activating unfolded protein response[J]. Dna&Cell Biology,2018,37(4):352-360.
• [16] Yuanyuan Z,Long L,Yazheng Z,et al. The myosinⅡinhibitor,blebbistatin,ameliorates FeCl3-induced arterial thrombosis via the GSK3β-NF-κB pathway[J]. International Journal of Biological Sciences,2017,13(5):630-639.
• [17] Zhengmao L,Fenzan W,Xie Z,et al. Valproate attenuates endoplasmic reticulum stress-induced apoptosis in SH-SY5Y cells via the AKT/GSK3βsignaling pathway[J]. International Journal of Molecular Sciences,2017,18(2):315-328.
• [18] Tianchi C,Hechen H,Yuan Z,et al. HJURP promotes hepatocellular carcinoma proliferation by destabilizing p21 via the MAPK/ERK1/2 and AKT/GSK3βsignaling pathways[J].Journal of Experimental&Clinical Cancer Research,2018,37(1):193-205.