胞外热休克蛋白70在急性胰腺炎肺损伤中的调节作用  

The role of extracellular HSP70 in regulating lung injury in acute pancreatitis

作　　者：李影[1] 戴胜杰 孙学成[2] 孔鸿儒 陈咨苗[3] 孙洪伟[2] LI Ying;DAI Shengjie;SUN Xuecheng;KONG Hongru;CHEN Zimiao;SUN Hongwei(Department of Hepatopancreatobiliary Surgery,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;Department of Operating Room,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;Department of Endocrinology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]温州医科大学附属第一医院手术室,浙江温州325015 [2]温州医科大学附属第一医院肝胆胰外科,浙江温州325015 [3]温州医科大学附属第一医院内分泌科,浙江温州325015

出　　处：《温州医科大学学报》2022年第3期216-221,共6页Journal of Wenzhou Medical University

基　　金：温州市基础性科研项目(Y20180226,Y20180103,Y20180077);浙江省医药卫生学科平台(青年人才)项目(2018RC056)。

摘　　要：目的:探讨胞外热休克蛋白70(HSP70)在急性胰腺炎(AP)并发急性肺损伤过程中的调节作用。方法:构建不同胞外HSP70表达量的相关AP小鼠模型,通过检测胰腺含水量、胰腺和肺脏组织HE染色、酶联免疫吸附测定(ELISA)实验、肺脏组织转录组测序、RT-PCR等实验,观察不同胞外HSP70表达水平在AP急性肺损伤中所起的作用。结果:在胰腺含水量、胰腺和肺脏组织HE染色实验中,较高的胞外HSP70水平表现为更高的胰腺含水量,胰腺组织和肺脏组织水肿更明显(P<0.05);在ELISA实验中,较高的胞外HSP70水平亦伴随着较高的肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)水平(P<0.05);在肺脏组织转录组测序实验中,AP组导致的基因表达量改变现象最显著,且其主要影响ECM-receptor interaction、Cytokinecytokine receptor interaction、Focal adhesion、PI3K/Akt等信号通路,改变细胞黏附功能。在RT-PCR实验中,改变最为显著的相关基因的表达量改变与转录组测序结果相一致。结论:胞外HSP70可加重AP肺损伤,并可能通过ECM-receptor interaction、Cytokine-cytokine receptor interaction、Focal adhesion、PI3K/Akt等信号通路发挥作用。Objective: To investigate the regulating role of extracellular heat shock protein 70(HSP70) in acute pancreatitis complicated with acute lung injury. Methods: The mouse models of acute pancreatitis with different expression of extracellular HSP70 were constructed. The role of extracellular HSP70 in acute pancreatitis and acute lung injury was observed by detecting pancreatic water content, HE staining of pancreas and lung tissue,enzyme linked immunosorbent assay(ELISA), transcriptome sequencing of lung tissue and RT-PCR. Results:In the experiments of pancreatic water content and HE staining of pancreatic and lung tissues, higher level of extracellular HSP70 showed higher pancreatic water content, and more obvious edema of pancreatic and lung tissues(P<0.05). In the ELISA experiment, higher level of extracellular HSP70 was also accompanied by higher level of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)(P<0.05). In the lung tissue transcriptional sequencing experiment, the gene expression change caused by acute pancreatitis was the most significant, which mainly affected the signal pathways such as ECM-receptor interaction, Cytokine-cytokine receptor interaction,Focal adhesion and PI3K/Akt and thereby changed the function of cell adhesion. In the RT-PCR experiment,the expression of the most significantly changed related genes was consistent with the results of transcriptome sequencing. Conclusion: This study shows that extracellular HSP70 can aggravate lung injury in acute pancreatitis and may play a role through such signal pathways as ECM-receptor interaction, Cytokine-cytokine receptor interaction, Focal adhesion and PI3K/Akt.

关 键 词：急性胰腺炎 热休克蛋白70 肺损伤 

分 类 号：R576[医药卫生—消化系统]