摘要
目的 观察急性胰腺炎时肺内肿瘤坏死因子 α(TNF α)基因表达及细胞凋亡的状况 ,并探讨其与肺损伤的关系。方法 以不同浓度牛磺胆酸钠液逆行胰胆管注射造成大鼠急性水肿性胰腺炎(AEP)与急性坏死性胰腺炎 (ANP)两种模型 ,测定血浆TNF α水平 ;半定量RT PCR及免疫组化检测肺组织内TNF α基因表达水平 ;TUNEL法结合激光扫描共聚焦显微镜检测肺内细胞凋亡的情况。结果 诱导AEP后肺内TNF αmRNA及其蛋白的表达呈短暂的一过性增强 ,这种表达在ANP组则更为强烈与持久 ,与ANP组发生明显肺损伤相关 (P <0 .0 5 )。肺内细胞凋亡指数 (‰ )在AEP组呈一过性下降 ,在ANP组呈持续下降 ,其变化与肺损伤严重程度及肺内TNF αmRNA水平呈负相关 (P <0 .0 5 )。结论 ANP时肺内TNF α基因转录表达过度上调 ,代表一种超强的全身炎症反应即全身炎症反应综合征 (SIRS) ,与肺损伤的发生有关。同时 ,肺内浸润的炎细胞 (主要是中性粒细胞 )发生延迟凋亡 ,可能在肺损伤进程中起作用 ,而TNF α的过度生成是中性粒细胞延迟凋亡的部分原因。
Objective To investigate the intrapulmonary expression of tumor necrosis factor-α (TNF-α) gene during acute pancreatitis, as well as correlation between TNF-α and lung injury seen in many patients undergoing acute necrotizing pancreatitis (ANP). Methods Ninety SD rats were divided into three groups randomly. Acute edematous pancreatitis(AEP) and ANP were induced by retrograde infusion of sodium taurocholate (0.5% and 5%) into biliopancreatic duct respectively. Animals in the last group only underwent sham-operation. All the animals were sacrificed at certain time, plasma level of amylase and TNF-α was assessed. Intrapulmonary expression of TNF-α mRNA and TNF-α protein was detected by semi-quantitative RT-PCR and immunohisto- chemistry. Cell apoptosis was assessed by TUNEL method. Results Intrapulmonary expression of TNF-α mRNA was much stronger and more sustained in ANP group than that in AEP group (P<0.05), while no TNF-α mRNA could be detected in lung tissue from those undergoing sham- operation. Changes of production of TNF-α protein by pulmonary macrophage and plasma level of TNF-α were similar to the expression of its gene. Lung damage in ANP group was more serious than that in AEP group, and score of lung injury correlated well with TNF-α expression in this two groups (P<0.05). Apoptosis index (AI) appeared to decrease transiently in AEP group and decrease continuously in ANP group. Apoptosis is rarely detected in a large number of inflammatory cells aggregating in lung tissue during ANP, this is the cause of marked reduction of AI. The change of AI had a negative correlation with intrapulmonary expression of TNF-α mRNA and histopathological score in the two groups respectively. Conclusions Overwhelm expression of TNF-α gene in lung tissue contributes to the serious lung injury during ANP, and overproduction of TNF-α may partially explain the significantly delayed apoptosis of neutrophils after ANP is induced.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2002年第1期22-25,共4页
Chinese Journal of Digestion