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胆道外引流通过上调血红素加氧酶-1保护重症急性胰腺炎大鼠的多器官损伤。

Biliary tract external drainage protects against multiple organs injuries of severe acute pancreatitis rats via heme oxygenase-1 upregulation.

作者信息

Wang Jin-Long, Chen Ying, Song Xiao-Qing, Lu Mei-Ling, Zhao Bing, Ma Li, Chen Er-Zhen, Mao En-Qiang

机构信息

Department of Emergency Intensive Care Unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.

出版信息

Pancreatology. 2017 Mar-Apr;17(2):219-227. doi: 10.1016/j.pan.2017.01.012. Epub 2017 Feb 1.

Abstract

OBJECTIVE

To investigate the effect of biliary tract external drainage (BTED) on severe acute pancreatitis (SAP) in rats and the relationship with heme oxygenase-1 (HO-1) pathway.

METHODS

Thirty SD rats weighing 250-300 g were randomly assigned into five groups (n = 6): sham surgery (SS) group, SAP group, SAP + BTED group, SAP + zinc protoporphyrin IX (ZnPP) group, SAP + BTED + ZnPP group. The SAP model was induced via retrograde injection of 4% sodium taurocholate (1 mL/kg) into biliopancreatic duct through duodenal wall. BTED was performed by inserting a cannula into the bile duct of SAP rats. Tissue and blood samples were collected 24 h after surgery. Pathological changes in organs were scored. The level of amylase, alanine transaminase (ALT), aspartate aminotransferase (AST), diamine oxidase (DAO), lipopolysaccharide (LPS), myeloperoxidase (MPO) and ability to inhibit hydroxyl radical(·OH) in serum were measured. The expression of hemeoxygenase-1 (HO-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in tissues were analyzed by RT- PCR and western-blot.

RESULTS

Organs damage in SAP rats was significantly alleviated by BTED (p < 0.05). Compared to the SAP group, the serum level of amylase, ALT, AST, DAO, MPO, and LPS were significantly lower in the SAP + BTED group, and the ability to inhibit ·OH was significantly higher (p < 0.05). The BETD treatment led to a significant reduction of TNF-α, IL-6 level and a significant increase of HO-1 level in tissues than in SAP rats (p < 0.05). ZnPP significantly inhibited all above mentioned changes.

CONCLUSIONS

BTED protected multiple organs against SAP related injuries via HO-1 upregulation.

摘要

目的

探讨胆道外引流(BTED)对大鼠重症急性胰腺炎(SAP)的影响及其与血红素加氧酶-1(HO-1)通路的关系。

方法

将30只体重250 - 300 g的SD大鼠随机分为五组(n = 6):假手术(SS)组、SAP组、SAP + BTED组、SAP + 锌原卟啉IX(ZnPP)组、SAP + BTED + ZnPP组。通过经十二指肠壁向胆胰管逆行注射4%牛磺胆酸钠(1 mL/kg)诱导建立SAP模型。通过将套管插入SAP大鼠胆管进行BTED操作。术后24 h采集组织和血液样本。对器官病理变化进行评分。检测血清淀粉酶、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、二胺氧化酶(DAO)、脂多糖(LPS)、髓过氧化物酶(MPO)水平及抑制羟自由基(·OH)的能力。采用RT-PCR和蛋白质印迹法分析组织中血红素加氧酶-1(HO-1)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达。

结果

BTED显著减轻了SAP大鼠的器官损伤(p < 0.05)。与SAP组相比,SAP + BTED组血清淀粉酶、ALT、AST、DAO、MPO和LPS水平显著降低,抑制·OH的能力显著升高(p < 0.05)。与SAP大鼠相比,BTED治疗使组织中TNF-α、IL-6水平显著降低,HO-1水平显著升高(p < 0.05)。ZnPP显著抑制了上述所有变化。

结论

BTED通过上调HO-1保护多器官免受SAP相关损伤。

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