柴黄清胰活血方对重症急性胰腺炎肺损伤模型大鼠JNK/P38MAPK信号通路的影响  

Effect of Chaihuang Qingyi Huoxue Formula on the JNK/P38MAPK Signaling Pathway in Rats with Severe Acute Pancreatitis and Lung Injury

作　　者：余霞 刘建琴 姜朝丽 仁德芳 李丽 赵龙 李志 Yu Xia;Liu Jianqin;Jiang Chaoli;Ren Defang;Li Li;Zhao Long;Li Zhi(College of Integrated Chinese and Western Medicine,Southwest Medical University,Luzhou 646000;Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000)

机构地区：[1]西南医科大学中西医结合学院,泸州646000 [2]西南医科大学附属中医医院,泸州646000

出　　处：《中药药理与临床》2021年第5期85-92,共8页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省科技计划项目(编号:2019YFS0163);泸州市人民政府-西南医科大学科技战略合作项目(编号:2018LZXNYD-YL03);西南医科大学-西南医科大学附属中医医院联合课题(编号:2018XYLE-007);西南医科大学-西南医科大学附属中医医院联合课题(编号:2018XYLE-024)。

摘　　要：目的:研究柴黄清胰活血方对重症急性胰腺炎肺损伤模型大鼠的影响及其可能的机制。方法:将大鼠随机分为正常对照组、模型对照组、柴黄清胰活血方4.8 g/kg组,每组32只。以5%牛磺胆酸钠制备重症急性胰腺炎(SAP)模型,各组灌胃相应药物或生理盐水,每6 h/次,术后6 h、12 h、24 h、48 h采集各组大鼠动脉血和肺组织。生化法检测各组大鼠血清淀粉酶(AMY)、脂肪酶(LIP)活力;血气分析检测氧分压[P(O_(2))]、二氧化碳分压[P(CO_(2))]并计算氧合指数(OI);HE染色观察肺组织病理变化;免疫组化法检测肺组织肿瘤坏死因子-α(TNF-α)、白介素1β(IL-1β)、细胞间粘附分子-1(ICAM-1)、水通道蛋白-1(AQP-1)、C-Jun氨基末端激酶(JNK)、P38丝裂原活化蛋白激酶(P38MAPK)蛋白的表达;Western Blot法检测肺组织JNK、P38MAPK、p-JNK、p-P38MAPK蛋白表达及其比值;RT-PCR法检测肺组织Icam-1、Aqp-1、Jnk1、P38mapk mRNA的表达。结果:与正常对照组比较,模型对照组大鼠肺组织出现明显病理损伤,AMY、LIP活力、P(CO_(2))明显升高,TNF-α、IL-1β、ICAM-1、JNK、P38MAPK蛋白表达明显升高(P<0.05),P(O_(2))、OI明显降低,AQP-1蛋白表达明显下调(P<0.05)。p-JNK及JNK、p-P38MAPK及P38MAPK蛋白及磷酸化水平的表达均明显上调(P<0.05),Icam-1、Jnk1、P38mapk mRNA表达上调、Aqp-1 mRNA表达下调(P<0.05);与模型对照组比较,柴黄清胰活血方4.8 g/kg组大鼠肺组织病理损伤明显缓解,AMY、LIP活力、P(CO_(2))明显降低,TNF-α、IL-1β、ICAM-1、JNK、P38MAPK蛋白表达明显下调(P<0.05),P(O_(2))、OI明显升高,AQP-1蛋白表达明显上调(P<0.05)。p-JNK及JNK、p-P38MAPK及P38MAPK蛋白及磷酸化水平均明显下调(P<0.05),Icam-1、Jnk1、P38mapk mRNA表达均明显下调、Aqp-1 mRNA表达明显上调(P<0.05)。结论:柴黄清胰活血方可能通过抑制JNK/P38MAPK信号通路作用于SAP肺损伤模型大鼠。Objective:To investigate the effect of Chaihuang Qingyi Huoxue Formula(CHQYHX)on severe acute pancreatitis(SAP)and lung injury in rats and its underlying mechanism.Methods:Rats were randomly divided into a normal control group,a model group,and a CHQYHX(4.8 g/kg)group,with 32 rats in each group.The SAP model was induced by 5%sodium taurocholate.Rats were administered with corresponding drugs or normal saline once every 6 h.The arterial blood and lung tissues of rats in each group were collected 6,12,24,and 48 h after surgery.The activities of serum amylase(AMY)and lipase(LIP)were detected by the biochemical assay.The partial pressure of oxygen P(O_(2))and partial pressure of carbon dioxide P(CO_(2))were detected by blood gas analysis and the oxygenation index(OI)was calculated.HE staining was used to observe pathological changes of lung tissues.The expression of tumor necrosis factor-α(TNF-α),interleukin 1β(IL-1β),intercellular adhesion molecule-1(ICAM-1),aquaporin-1(AQP-1),C-jun N-terminal kinase(JNK),and P38 mitogen-activated protein kinase(P38 MAPK)in lung tissues was detected by immunohistochemistry.The expression and ratios of JNK,P38 MAPK,p-JNK,and p-P38 MAPK in lung tissues were detected by Western blot.RT-PCR was used to detect the mRNA expression of ICAM-1,AQP-1,JNK1,and P38 MAPK in lung tissues.Results:Compared with the normal control group,the model group showed obvious pathological damage in lung tissues,potentiated activities of AMY and LIP,increased P(CO_(2)),elevated protein expression of TNF-α,IL-1β,ICAM-1,JNK,and P38 MAPK(P<0.05),decreased P(O_(2))and OI,down-regulated AQP-1 protein expression(P<0.05),up-regulated protein expression and phosphorylation of p-JNK,JNK,p-P38 MAPK,and P38 MAPK(P<0.05),increased mRNA expression of ICAM 1,JNK 1,and P38 MAPK,and dwindled mRNA expression of AQP-1(P<0.05).Compared with the model group,the CHQYHX group displayed relieved pathological damage in lung tissues,blunted AMY and LIP activities,decreased P(CO_(2)),down-regulated protein expression of TNF-α,I

关 键 词：柴黄清胰活血方 重症急性胰腺炎 肺损伤 C-Jun氨基末端激酶/P38丝裂原活化蛋白激酶信号通路 

分 类 号：R285.5[医药卫生—中药学]