基于PI3K/AKT/NF-κB信号通路探讨自拟英黄汤对脓毒症大鼠的保护作用  

Based on PI3K/AKT/NF-κ exploring the protective effect of self-made Yinghuang Decoction on sepsis rats through the B signaling pathway

作　　者：郭军利 陶愚磊 郑佳丽 梅建强[2] 陈分乔[2] 许文忠[2] Guo Junli;Tao Yulei;Zheng Jiali;Mei Jianqiang;Chen Fenqiao;Xu Wenzhong(Graduate School of Hebei University of Traditional Chinese Medicine,Hebei Province,Shijiazhuang 050091,China;不详)

机构地区：[1]河北中医学院研究生学院,石家庄050091 [2]河北省中医院急诊科,石家庄050000

出　　处：《疑难病杂志》2023年第11期1197-1203,1209,共8页Chinese Journal of Difficult and Complicated Cases

基　　金：2022年河北省自然科学基金(H2022423369);2023年政府资助临床医学优秀人才项目(ZF2023159);国家中医药管理局梅建强全国名老中医药专家传承工作室(国中医药办人教函〔2022〕75号)。

摘　　要：目的基于PI3K/AKT/NF-κB信号通路探讨英黄汤对脓毒症大鼠的保护作用。方法2022年8—12月于河北省中医药科学院附属医院动物实验室进行实验,将240只雄性SD大鼠按随机数字表法分为假手术组、模型组、地塞米松组、英黄汤低剂量组、英黄汤中剂量组、英黄汤高剂量组,每组40只。每组20只大鼠用于观察7 d内生存率,剩余20只大鼠造模给药72h后,通过检测凝血相关指标、肺组织湿重/干重(W/D)比值、BALF中总蛋白含量、肝肾功能相关指标,观察英黄汤的干预作用;通过HE染色观察英黄汤对肺、肝、肾组织的病理变化;通过检测血清中IL-6、IL-1β、TNF-α水平以及肺组织中IL-6、IL-1β、TNF-α基因表达,观察英黄汤对炎性因子的影响;通过Western-blot方法检测英黄汤对肺组织中PI3K/AKT/NF-κB通路的影响。结果英黄汤中高剂量组大鼠生存率均高于地塞米松组。造模给药72 h后,与假手术组相比,模型组大鼠血清中PLT、Fib含量显著降低,PT、APTT、TT时间显著延长;BALF中总蛋白含量、W/D比值、ALT、AST、SCr、BUN水平显著增加;肺、肝、肾组织病理明显损伤;血清中IL-6、IL-1β、TNF-α水平及肺组织中IL-6、IL-1β、TNF-α基因水平显著增高;p-PI3K/PI3K、p-AKT/AKT、p-P65/P65蛋白比值均显著增高。与模型组相比,地塞米松组、英黄汤各剂量组大鼠血清中PLT、Fib含量显著增加(F/P=39.161/<0.001、11.233/<0.001),PT、APTT时间显著缩短(F/P=32.933/<0.001、22.177/<0.001);BALF中总蛋白、W/D比值、ALT、AST、SCr、BUN水平显著降低(F/P=27.160/<0.001、29.291/<0.001、20.553/<0.001、10.567/<0.001、28.450/<0.001、11.374/<0.001);肺、肝、肾组织损伤明显改善;血清中IL-6、IL-1β、TNF-α水平显著降低(F/P=26.967/<0.001、38.238/<0.001、34.333/<0.001),肺组织中IL-6、IL-1β、TNF-α基因表达降低;p-PI3K/PI3K、p-AKT/AKT、p-P65/P65比值显著减小(F/P=22.826/<0.001、21.432/<0.001、83.294/<0.001)。结论�Objective To investigate the protective effect of Yinghuang Decoction on septic rats based on PI3K/AKT/NF-κB signaling pathway.Methods Two hundred and forty male SD rats were randomly divided into sham-operated group,model group,dexamethasone group,Yinghuang Decoction low-dose group,Yinghuang Decoction medium-dose group and Yinghuang Decoction high-dose group,40 rats in each group.Twenty rats in each group were used to observe the survival rate within 7 days.After the remaining 20 rats were molded and administered for 72h,the therapeutic effects of YingHuang Decoction were observed by detecting the coagulation-related indexes,wet weight/dry weight ratio of lung tissues,total protein content in BALF,and liver and kidney function-related indexes;the pathological changes of YingHuang Decoction on lung,liver and kidney tissues were observed by HE staining;the levels of IL-6,IL-1β and TNF-α in serum and the levels of IL-6,The effect of YingHuang Decoction on inflammatory factors was observed by detecting serum levels of IL-6,IL-1β,TNF-α and gene expression of IL-6,IL-1β and TNF-α in lung tissues;the effect of Yinghuang Decoction on PI3K/AKT/NF-κB pathway in lung tissues was detected by Western-blot method.Results The survival rate of septic rats in Decoction medium-dose group and high-dose group was higher than that in dexamethasone group.After modeling administration for 72h,compared with the sham-operated group,the serum levels of PLT and Fib in the model group rats were significantly reduced,and the PT,APTT and TT times were significantly prolonged;the levels of total protein,W/D ratio,ALT,AST,SCr and BUN in BALF were significantly increased;the histopathology of lung,liver and kidney were significantly damaged;the serum levels of IL-6,IL-1β,TNF-α,IL-6,IL-1β,TNF-α gene levels were significantly increased in lung tissue;p-PI3K/PI3K,p-AKT/AKT,p-P65/P65 protein ratios were increased.Compared with the model group,the serum levels of PLT and Fib were significantly increased(F/P=39.161/0.000,11.233/0.000)and

关 键 词：脓毒症 英黄汤 炎性因子 PI3K/AKT/NF-κB信号通路 大鼠 

分 类 号：R631.2[医药卫生—外科学]