不同剂量升降散对脓毒症心肌P38MAPK信号转导通路干预作用的研究  

To study the intervention effect of different doses of Shengjiang San on p38MAPK signal transduction pathway in sepsis

作　　者：赵雷[1] 丁纯蕾[1] 蒋锦琪[2] 朱亮[1] 钱风华[1] 郭健[1] Zhao Lei;Ding Chun-lei;Jiang Jin-qi;Zhu Liang;Qian Feng-him;Guo Jian(Department of Emergency,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海交通大学附属胸科医院,上海200030

出　　处：《中国急救医学》2019年第12期1144-1148,共5页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金青年科学基金项目(81303101);上海市卫生计生系统重要薄弱学科建设项目(2016ZB0205-01)。

摘　　要：目的探讨升降散保护脓毒症心肌损伤的分子机制。方法雄性成年SD大鼠随机分为正常组、模型组、升降散低剂量组、升降散中剂量组、升降散高剂量组和P38MAPK抑制组。采用盲肠结扎穿孔术(cecal ligation and puncture,CLP)制备脓毒症大鼠模型,造模后4.8.12 h进行观察。升降散组于造模后2 h分别给予升降散冻干粉1.5 g/kg、3 g/kg、6 g/kg灌胃,正常组和模型组给予等量生理盐水灌胃。P38MAPK抑制组于造模前2 h分别给予P38MAPK抑制剂(SB203580)2 mg/kg腹腔皮下注射。腹主动脉留取血标本和心脏组织做相关检测。观察和检测各时间点大鼠病死率、血清白细胞介素-6(interleukin-6,IL-6)水平、肿瘤坏死因子-a(tumor necrosis factor-a,TNF-a)、p-p38MAPK蛋白水平,及p-p38MAPK mRNA、TNF-a mRNA、IL-6 mRNA、诱导型一氧化氮合酶mRNA(inducible nitric oxide synthase mRNA,iNOS mRNA)相对值水平变化。结果造模后各项检测指标均有所上升。升降散中剂量组8、12 h TNF-a水平均明显低于模型组(P=0.024,P<0.001);与模型组比较,升降散髙剂量组各时间点TNF-a均明显下降(P<0.001)。升降散低剂量组8 h IL-6水平低于模型组(P=0.022);升降散中剂量、高剂量组各时间点IL-6水平明显低于模型组(P<0.001)。升降散中、高剂量组各时间点p-P38MAPK蛋白表达较模型组降低。升降散中剂量组8、12 h p-P38 MAPK mRNA较模型组均明显下降(P<0.001);高剂量组各时间点p-P38MAPK mRNA均较模型组有所下降(P<0.001)o升降散中剂量组8J2 hTNF-a mRNA较模型组下降(P=0.018<0.001);升降散高剂量组各时间点TNF-a mRNA均较模型组下降(P<0.001)。升降散中剂量组8、12 h IL-6 mRNA较模型组下降(P=0.008,P<0.001);升降散高剂量组4、8、12 h IL-6 mRNA较模型组下降(P=0.036,P<0.001,P<0.001)。升降散低剂量组12 h iNOS mRNA较模型组下降(P=0.043);中剂量组8、12 h iNOS mRNA较模型组下降(P<0.001,P=0.002);升降散高剂量组各时间点iNOS mRNA�Objective To investigate the protective effect of traditional Chinese medicine Shengjiang San against myocardical injury and its molecular mechanism.Methods Male adult SD rats were randomly divided into normal group,model group,low一dose Shengjiang San group,medium-dose Shengjiang San group,high一dose Shengjiang San group and p38MAPK inhibition group.Septic rat models were set up by cecal ligation and puncture(CLP).The rats were observed at 4,8,12 h after operation.The Shengjiang San group was given at a dosage of 1.5 g/kg,3 g/kg,6 g/kg at 2 h after the modeling,respectively.The rats in normal group and the model group were given the same amount of normal saline.The p38MAPK inhibition group was given subcutaneously intraperitoneal injection of p38MAPK inhibitor(SB203580)2 mg/kg at 2 h before model establishment.Blood samples from the abdominal aorta and heart tissue were collected.The mortality was recorded,serum interleukin-6(IL-6)level,tumor necrosis factor-a(TNF-a)and p-p38MAPK protein levels at various time points,and the relative levels of p-p38MAPK mRNA,TNF一a mRNA,IL-6 mRNA and inducible nitric oxide synthase一mRNA(iNOS mRNA)were detected.Results After the modeling,the detected indicators increased.TNF一a levels at 8,12 h in the medium-dose group were significantly lower than those in the model group(P=0.024,P<0.001),and the levels of TNF-a at different time points in the high一dose group decreased significantly compared with the model group(P<0.001).IL-6 level at 8 h in the low一dose group was lower than that in the model group(P=0.022),and the IL-6 level at different time points in the medium-dose group and high一dose group was significantly lower than that in the model group(P<0.001).The expression of p-p38MAPK protein at different time points in the medium-dose group and high一dose group decreased compared with the model group.The expression of p-p38MAPK mRNA at 8,12 h in the medium-dose group decreased significantly compared with model group(P<0.001),but those at different time points in high

关 键 词：脓毒症 心肌损伤 升降散 p38丝裂原活化蛋白激酶(P38MAPK) 

分 类 号：R285.5[医药卫生—中药学]