CAJ | 학술논문

目的：探讨急性胰腺炎大鼠肠上皮细胞αSNAP 表达及其与肠黏膜通透性的关系。方法采用逆行胰胆管注射3.8%和0.5%的牛黄胆酸钠溶液的方法制备重症急性胰腺炎模型和轻症急性胰腺炎模型。并分别于1d、2d、3d处死动物，比较各组的胰腺病理改变、肠黏膜病理改变；肠道通透性的变化以及肠上皮occludin蛋白和αSNAP蛋白的表达状况。结果 SO组胰腺组织无明显变化；肠绒毛形态正常；1 d、2 d、3 d 肠组织病理评分（1∶1∶1）；SO 组血清 TNF-α、内毒素水平无明显变化；肠道通透性为1 d，（11.08±4.22）μg/20 ml；2 d，（8.31±1.74）μg/20 ml；3 d，（16.50±8.83）μg/20 ml。MAP 组胰腺小叶排列松散、水肿，有少量炎性细胞浸润；1 d、2 d、3 d 肠组织病理评分分别为1.500±0.54、1.88±0.35、2.13±0.64；血清TNF-α、内毒素水平轻微升高，肠道通透性轻微升高[1 d：（75.39±34.40）μg/20 ml；2 d：（123.50±5.09）μg/20 ml；3 d：（66.11±9.48）μg/20 ml]。SAP 组胰腺组织坏死、大量炎症细胞浸润；肠绒毛出现明显水肿、倒伏、萎缩，肠上皮细胞坏死、脱落，1 d、2 d、3 d肠组织病理评分分别为3.38±0.52、4.13±0.84、5.13±0.84；SAP 组大鼠血清 TNF-α、内毒素水平明显升；肠道通透性明显升高[1 d：（379.34±25.38）μg/20 ml；2 d：（586.52±57.35）μg/20 ml；3 d：（489.76±105.36）μg/20 ml]；SAP 组大鼠肠上皮细胞occludin和αSNAP蛋白表达明显下调。结论急性胰腺炎早期，特别是SAP，常伴随肠黏膜通透性增加、血清TNF-α和内毒素水平提高，进一步诱发全身炎症反应综合征（SIRS）和多器官功能障碍综合征（MODS）。肠上皮细胞αSNAP表达下调，进而导致occludin表达降低，进而引起肠黏膜屏障通透性的增加，进一步诱发SIRS和MODS。
목적：탐토급성이선염대서장상피세포αSNAP 표체급기여장점막통투성적관계。방법채용역행이담관주사3.8%화0.5%적우황담산납용액적방법제비중증급성이선염모형화경증급성이선염모형。병분별우1d、2d、3d처사동물，비교각조적이선병리개변、장점막병리개변；장도통투성적변화이급장상피occludin단백화αSNAP단백적표체상황。결과 SO조이선조직무명현변화；장융모형태정상；1 d、2 d、3 d 장조직병리평분（1∶1∶1）；SO 조혈청 TNF-α、내독소수평무명현변화；장도통투성위1 d，（11.08±4.22）μg/20 ml；2 d，（8.31±1.74）μg/20 ml；3 d，（16.50±8.83）μg/20 ml。MAP 조이선소협배렬송산、수종，유소량염성세포침윤；1 d、2 d、3 d 장조직병리평분분별위1.500±0.54、1.88±0.35、2.13±0.64；혈청TNF-α、내독소수평경미승고，장도통투성경미승고[1 d：（75.39±34.40）μg/20 ml；2 d：（123.50±5.09）μg/20 ml；3 d：（66.11±9.48）μg/20 ml]。SAP 조이선조직배사、대량염증세포침윤；장융모출현명현수종、도복、위축，장상피세포배사、탈락，1 d、2 d、3 d장조직병리평분분별위3.38±0.52、4.13±0.84、5.13±0.84；SAP 조대서혈청 TNF-α、내독소수평명현승；장도통투성명현승고[1 d：（379.34±25.38）μg/20 ml；2 d：（586.52±57.35）μg/20 ml；3 d：（489.76±105.36）μg/20 ml]；SAP 조대서장상피세포occludin화αSNAP단백표체명현하조。결론급성이선염조기，특별시SAP，상반수장점막통투성증가、혈청TNF-α화내독소수평제고，진일보유발전신염증반응종합정（SIRS）화다기관공능장애종합정（MODS）。장상피세포αSNAP표체하조，진이도치occludin표체강저，진이인기장점막병장통투성적증가，진일보유발SIRS화MODS。
Objective To investigate the expression of αSNAP in rats with acute pancreatitis and its relationship with intestinal permeability. Methods Seventy-two Sprague Dawley rats were randomized into groups of SO, MAP and SAP. MAP and SAP models of rats was induced by retrograde injection of sodium taurocholate into the biliopancreatic duct in a pressure- and volume-controlled manner over 10 min. All experimental animals were killed in 1 d, 2 d and 3 d for detecting pancreatic pathological condition, change of intestinal villi pathology and intestinal permeability, as well as the expression of occludin and αSNAP in the intestinal epithelial cells. Results Pancreatic pathology of SO group showed that pancreatic tissue was normal;Intestinal villi morphology also was normal;intestinal pathology scores were 1∶1∶1;the level of serum TNF-αand endotoxin in the SO rats have no increase;Intestinal permeability in SO group [1 d:(11.08±4.22)μg/20 ml;2 d:(8.31±1.74)μg/20 ml; 3 d: (16.50±8.83)μg/20 ml].Pancreatic pathology of MAP group showed that pancreatic lobule arranged loosely edema a few of inflammatory cells infiltrate;intestinal pathology scores were 1.500±0.54;1.88±0.35; 2.13±0.64; the level of serum TNF-α and endotoxin in the SO rats Moderately elevated; Intestinal permeability in SO group[1 d, (75.39±34.40)μg/20 ml; 2 d, (123.50±5.09)μg/20 ml; 3 d, (66.11±9.48)μg/20 ml]. Pancreatic pathology in SAP group showed that pancreatic tissue necrosis, a large amount of inflammatory cells infiltrate;Intestinal villi marked edema, lodging, atrophy, intestinal epithelial cells necrosis and abscission in SAP rats; serum TNF-α and endotoxin in the SAP rats markedly elevated; Intestinal permeability in SAP group markedly elevated [1 d: (379.34±25.38)μg/20 ml; 2 d: (586.52±57.35)μg/20 ml; 3 d: (489.76±105.36)μg/20 ml]. Immunofluorescence and Western blot showed that compared with the SO, MAP groups, expression of occluding andαSNAP in rat intestinal epithelial cells were markedly downregulated in SAP group. Conclusions In early stage of acute pancreatitis, particularly SAP, often associated with increased permeability of the intestinal epithelium, and serum levels of TNF-α and endotoxin levels are increased. αSNAP downregulation in intestinal epithelial cells might reduce occludin expression and cause increased permeability of the intestinal barrier, induced MODS and SIRS.