大鼠急性胰腺炎相关肺损伤肺脏内源性H2S／CSE体系的变化  

Change of endogenous hydrogen sulfide/cystathionine-γ-lyase system in acute lung injury induced by acute pancreatitis in rats

作　　者：王智刚[1] 江勇[2] 吴宝强[2] 孙振棣[2] 

机构地区：[1]江苏省常州市第一人民医院呼吸内科,213003 [2]江苏省常州市第一人民医院肝胆外科,213003

出　　处：《国际呼吸杂志》2011年第22期1716-1720,共5页International Journal of Respiration

基　　金：常州市科学技术局应用基础研究计划指导性项目（CY20119002）

摘　　要：目的观察急性胰腺炎相关肺损伤肺组织巾内源性硫化氢（H2S）/胱硫醚γ-裂解酶（CSE）体系的变化以及CSE抑制剂炔丙基甘氨酸（PAG）对急性胰腺炎相关肺损伤的影响。方法54只SD大鼠被随机分为3组。①胰腺炎组：向胆总管中注射5％牛黄胆酸钠建立大鼠急性胰腺炎相关肺损伤模型；②药物=F预组：在胰腺炎组的基础上，造模后1h腹腔注射PAG；⑧对照组为假手术组。每组取造模后3h、6h、坨h三个时点切取肺脏组织，分别采用HE病理检测，荧光定量PCR检测肺组织CSE及肿瘤坏死因子α（TNF-α）在mRNA水平的表达情况；经心脏采血，去蛋白法检测血清巾H2S含量。结果药物干预组较胰腺炎组组织学肺间质水肿及肺泡水肿、出血均有改善；造模后6h，胰腺炎组肺组织中CSEmRNA的相对表达量达到峰值，与其他2个时段相比具有显著差异（P〈0．05）；造模后12h，胰腺炎组CSEmRNA的相对表达量无明显升高，TNF-αmRNA的相对表达量较对照组升高（P〈0．05）。药物十预组中，造模后3h和6hCSEmRNA的相对表达量低于胰腺炎组（P〈0．05），造模后6hTNFumRNA的相对表达量低于胰腺炎组（P〈20．05），其余组差异无显著性。造模后3个时点，胰腺炎组较对照组血H2s浓度均升高，药物干预组造模后6h和12h血清H2S浓度低于胰腺炎组（P值均〈0．05）。结论急性胰腺炎相关肺损伤早期，H2S／CSE体系上调并加重了肺损伤；CSE合成酶抑制剂PAG可以降低血液巾H2S浓度，并改善肺脏的病理学评分；H2S／CSE体系可能是通过TNF-α来介导胰腺炎相关肺榻伤．Objective To explore the chang of hydrogen sulfide （HzS）/cystathionine-γ lyase （CSE） system in lung tissues of rats with acute pancreatitis associated lung injury and the effect of propargylglycine （PAG,CSE inhihitor） on acute pancreatitis associated lung injury. Methods 54 SD rats were radomly divided into three groups. Acute pancreatitis group was induced by injection of sodium deoxycholate into the common bile duct. Drug intervention group was made by intraperitoneal injection of PAG on the basis of acute pancreatitis group. Control group was made by sham operation. At 6, 12 and 24 hours after operation, each lung specimen was given pathological examination by HE staining and fluorescence quantitative PCR detection of expression of CSE and tumor necrosis factor -α （TNF-α） mRNA. The content of H2S in serum was analyzed by deproteinization. Results Control group showed normal lung tissue. In acute pancreatitis group, at 12h the gross specimen showed brown areas of atelectasis, and small quantity of pleural effusion. By light microscope, quantity of infiltration of inflammatory cells and exudates were visible in pulmonary interstitial, alveolar and bronchial. In drug intervention group, exudates and bleeding in alveolar and bronchial decreased. In acute paneteatitis group,at 6h the expression of CSE mRNA reached peak and was higher than that in other two groups （ P〈0.05）. At 3h and 6h the relative expression level of CSE gene was higher than that in control group （ P 〈 0.05）, and at 3h,6h and 12h the relative expression level of TNF-α gene was higher than that in control group （ P 〈0.05）. In drug intervention group,at 3h and 6h the relative expression level of CSE gene was lower than that in acute pancteatitis group （ P 〈0.05）, and at 6h the relative expression level of TNF-α gene was lower than that in acute pancteatitis group （ P 〈0.05）. In acute pancteatitis group, at 3h, 6h and 12h the serum concentration of H2S was higher than that in control group （ P 〈

关 键 词：急性胰腺炎相关肺损伤 胱硫醚γ裂解酶 硫化氖 肿瘤坏死因子Α 

分 类 号：R576[医药卫生—消化系统]