目的:探讨四氢化吡咯烷二硫代氨基甲酸酯(PDTC)对急性坏死性胰腺炎(ANP)大鼠急性肺损伤的影响。方法:36只成年SD大鼠随机均分为:假手术组,ANP组,PDTC预处理组。ANP模型采用逆行胰胆管注射5%牛磺胆酸钠的方法,PDTC预处理组在造模前l h腹腔注射PDTC(30 mg/kg)。术后6 h处死动物,经支气管肺泡灌洗获取肺泡巨噬细胞(AMs),用流式细胞仪检测AMs凋亡情况,免疫组化和Western blot法测定AMs中NF-κB和CYLD活性水平;检测支气管肺泡灌洗液(BALF)中TNF-α和IL-1β含量;同时行肺组织病理学检查和肺组织髓过氧化物酶(MPO)水平检测。结果:假手术组肺组织未见病理改变,ANP组和PDTC预处理组肺组织均出现充血、水肿、炎性渗出等病理改变,但PDTC预处理组病变程度轻与ANP组;ANP组肺组织的MPO活性,以及BALF的TNF-α,IL-1β含量较假手术组明显升高(均P<0.05),而PDTC预处理组上述指标的升高被明显抑制,与ANP组比较,差异有统计学意义(均P<0.05);假手术组,ANP组,PDTC预处理组AMs凋亡率分别为(3.47±1.45)%,(1.16±0.31)%,(1.80±0.60)%,各组间差异有统计学意义(均P<0.05);免疫组化显示,AMs中的NF-κB在假手术组、ANP组、PDTC预处理组分别呈弱阳性、强阳性、中等阳性表达;假手术组,ANP组,PDTC预处理组AMs的NF-κB的相对表达量分别为0.08±0.03,0.18±0.06,0.13±0.04,各组间差异均有统计学意义(均P<0.05),3组CYLD的相对表达量分别为0.32±0.09,0.15±0.05,0.26±0.08,假手术组与ANP组间差异有统计学意义(P<0.05),但与PDTC预处理组间差异无统计学意义(P>0.05);ANP组,PDTC预处理组AMs中NF-κB与CYLD的表达活性均呈负相关(r=-0.708,r=-0.481,均P<0.05)。结论:PDTC可能通过抑制NF-κB的活化从而诱导ANP大鼠肺泡巨噬细胞凋亡,并增强NF-κB负性调控因子CYLD的表达,进而减轻肺损伤。 Objective: To investigate the effect of pyrrolidine dithiocarbamate (PDTC) on acute lung injury in rats with acute necrotizing pancreatitis (ANP). Methods: Thirty-six adult SD rats were randomly divided into sham operation group, ANP group and PDTC pretreatment group. In the ANP model, 5% sodium taurocholate was injected into the pancreatic duct through the retrograde cholangiopancreatography. PDTC (30 mg / kg) was intraperitoneally injected into the PDTC preconditioning group 1 h before modeling. Animals were sacrificed at 6 hours after operation. Alveolar macrophages (AMs) were obtained by bronchoalveolar lavage. The apoptosis of AMs was detected by flow cytometry. The levels of NF-κB and CYLD in AMs were detected by immunohistochemistry and Western blot. The contents of TNF-α and IL-1β in bronchoalveolar lavage fluid (BALF) were detected. The lung histopathological examination and the level of myeloperoxidase (MPO) were also detected. Results: There were no pathological changes in the lungs of the sham operation group. Pathological changes such as hyperemia, edema and inflammatory exudation occurred in both the ANP group and the PDTC pretreatment group, but the pathological changes were mild in the PDTC pretreatment group and in the ANP group. The activity of MPO and the levels of TNF-α and IL-1β in BALF were significantly higher than those in sham operation group (all P <0.05), while the increase of these indexes in PDTC pretreatment group was significantly inhibited. Compared with ANP group, the difference (3.47 ± 1.45)%, (1.16 ± 0.31)% and (1.80 ± 0.60)%, respectively, in the sham operation group, ANP group and PDTC pretreatment group Immunohistochemistry showed that NF-κB in AMs was weakly positive, strongly positive and moderately positive in the sham operation group, ANP group and PDTC pretreatment group, respectively; both of the two groups had significant difference (all P <0.05) The relative expression levels of NF-κB in AMs in the operation group, ANP group and PDTC pretreatment group were 0.08 ± 0.03,0.18 ± 0.06 and 0.13 ± 0.04, respectively (all P <0.05), 3 The relative expression levels of CYLD were 0.32 ± 0.09,0.15 ± 0.05,0.26 ± 0.08, respectively. There was significant difference between sham operation group and ANP group (P <0.05), but there was no significant difference between PDTC group and PDTC pretreatment group (P> 0.05); A. There was a negative correlation between NF-κB and CYLD expression in NP and PDTC pretreatment groups (r = -0.708, r = -0.481, all P <0.05). Conclusion: PDTC may induce the apoptosis of alveolar macrophages in ANP rats by inhibiting the activation of NF-κB and enhance the expression of CYLD, a negative regulator of NF-κB, thereby reducing lung injury.