HO-1在重症急性胰腺炎引起的肠黏膜损伤中的作用及其机制  

Effects and Mechanism of HO-1 in Intestinal Mucosal Injury Caused by Severe Acute Pancreatitis

作　　者：张井银 李医铭 姜英建 李洪波[1] 王江 张佃良[1] 

机构地区：[1]青岛大学附属青岛市立医院普外一科,山东 青岛 [2]青岛大学附属青岛市海慈医院神经内三科,山东 青岛

出　　处：《临床医学进展》2023年第2期1530-1537,共8页Advances in Clinical Medicine

摘　　要：目的:本研究旨在探究HO-1对SAP大鼠肠黏膜的保护作用及机制。方法:选取SPF级健康雄性SD大鼠32只,随机分为假手术组(SO组)、重症急性胰腺炎组(SAP组)、HO-1激活组(SAP + Hemin组)、HO-1抑制组(SAP + Znpp组),每组8只。采用5%牛磺胆酸钠逆行注入胆胰管的方法建立大鼠SAP模型,SO组胆胰管注入等量生理盐水。干预组大鼠分别在建模前24 h腹腔注射Hemin和Znpp,其余组腹腔注射等量生理盐水。各组大鼠在手术后24 h检测大鼠血清淀粉酶、TNF-α、IL-6、IL-10、DAO活性以及D-LA、FABP2和内毒素水平;检测回肠组织MDA含量以及SOD和GPX的活性水平;苏木精–伊红(HE)染色观察胰腺、回肠病理变化;免疫荧光染色检测HO-1及Occludin、ZO-1的表达情况;TUNEL检测肠上皮细胞凋亡水平。结果:SAP组大鼠血清AMY、TNF-α、IL-6、DAO活性以及D-LA、FABP2和内毒素水平明显高于SO组,IL-10显著低于SO组(均P < 0.05)。与SAP组相比,SAP + Hemin组显著增加HO-1的表达,减轻了SAP全身炎症反应、MDA含量以及SOD和GPX的活性明显降低,肠上皮细胞凋亡减少(均P < 0.05)。同时,上调HO-1的表达减轻了对肠紧密连接蛋白表达的抑制作用,血清DAO活性及D-LA、FABP2和内毒素水平显著降低(均P < 0.05)。相反,SAP + Znpp组则表现出相反的实验结果。结论:H0-1通过减轻炎症、氧化应激及抗凋亡的作用来减轻重症急性胰腺炎肠粘膜损伤。Objective: To investigate the protective effect and mechanism of HO-1 on intestinal mucosa in SAP rats. Methods: Thirty-two SPF-grade healthy male SD rats were selected and randomly divided into sham-operated group (SO group), severe acute pancreatitis group (SAP group), HO-1 activation group (SAP + Hemin group), and HO-1 inhibition group (SAP + Znpp group), eight rats in each group. The rat SAP model was established through retrograde injection of 5% sodium taurocholate into the biliopancreatic duct, and the SO group was injected with equal amounts of saline into the bili-opancreatic duct. Hemin and Znpp were injected intraperitoneally 24 h before modeling in the in-tervention group, while equal amounts of saline were injected intraperitoneally in the other group. At 24 hours after surgery, serum amylase, TNF-α, IL-6, IL-10, DAO, D-LA, FABP2 and endotoxin lev-els were measured in rats;the MDA content and the activity levels of SOD and GPX in ileal tissue were measured;Hematoxylin and eosin (HE) staining for pathological changes in the pancreas and ileum;Immunofluorescence staining detection of HO-1 and Occludin, ZO-1 expression;TUNEL de-tection of apoptosis level in intestinal epithelial cells. Results: The serum AMY, TNF-α, IL-6, DAO, D-LA, FABP2 and endotoxin levels of rats in SAP group were significantly higher than those in SO group, and IL-10 was significantly lower than that in SO group (all P < 0.05). Compared with the SAP group, the SAP + Hemin group significantly increased HO-1 expression, attenuated systemic in-flammatory response, MDA content, and significantly reduced SOD and GPX activities, and de-creased intestinal epithelial cell apoptosis (all P < 0.05). Meanwhile, upregulation of HO-1 expres-sion attenuated the inhibitory effect on intestinal tight junction protein expression, and serum DAO, D-LA, FABP2 and endotoxin levels were significantly reduced (all P < 0.05). However, the SAP + Znpp group showed the opposite experimental results. Conclusion: HO-1 attenuates intestinal mu-cosal injury in

关 键 词：血红素加氧酶-1 重症急性胰腺炎 肠黏膜屏障 凋亡 氧化应激 

分 类 号：R57[医药卫生—消化系统]