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富含甲烷的盐水通过抑制炎症反应、氧化应激和胰腺细胞凋亡缓解雨蛙肽诱导的急性胰腺炎。

Methane-rich saline alleviates cerulein-induced acute pancreatitis by inhibiting inflammatory response, oxidative stress and pancreatic apoptosis in mice.

机构信息

Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

Shanghai Key Laboratory of Molecular Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.

出版信息

Int Immunopharmacol. 2017 Oct;51:17-24. doi: 10.1016/j.intimp.2017.07.022. Epub 2017 Jul 29.

Abstract

BACKGROUND

Acute pancreatitis (AP) is a potentially life-threatening gastrointestinal disease involving intracellular activation of digestive enzymes and pancreatic acinar cell injury. The present study was performed to investigate whether methane-rich saline (MS) was involved in the regulation of AP.

METHODS

MS (16ml/kg) was administered at different dosing frequencies on mice with cerulein-induced AP. Serum amylase, lipase and histopathological changes in the pancreas tissue were measured. Serum cytokine TNFα, IL-6, IFNγ and IL-10 were detected by ELISA. The mRNA levels of these inflammatory cytokines in the pancreas were detected by real time-PCR. Myeloperoxidase (MPO) and superoxide dismutase (SOD) were determined using commercial kits. Apoptosis was assessed by immunohistochemistry and Western blot.

RESULTS

MS treatment reversed the increased serum level of amylase and lipase, alleviated the pathological damage in the pancreas, and decreased the expression of TNFα, IL-6, IFNγ and IL-10 in cerulean-induced AP mice. In addition, MPO was down-regulated and SOD was up-regulated in the MS treated pancreas, indicating that MS had an anti-oxidant effect against AP. Furthermore, MS protected pancreatic cells against cerulean-induced apoptosis and abolished cleaved caspase-3.

CONCLUSION

MS exerted anti-inflammatory, anti-oxidant and anti-apoptotic effects on cerulein-induced AP in mice and may proved to be a promising therapeutic agent for the clinical treatment of pancreatitis.

摘要

背景

急性胰腺炎(AP)是一种潜在危及生命的胃肠道疾病,涉及消化酶的细胞内激活和胰腺腺泡细胞损伤。本研究旨在探讨富含甲烷的盐水(MS)是否参与了 AP 的调节。

方法

在胆胰酶诱导的 AP 小鼠中,以不同的给药频率给予 MS(16ml/kg)。测定血清淀粉酶、脂肪酶和胰腺组织的组织病理学变化。通过 ELISA 检测血清细胞因子 TNFα、IL-6、IFNγ和 IL-10。通过实时 PCR 检测胰腺中这些炎症细胞因子的 mRNA 水平。使用商业试剂盒测定髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)。通过免疫组化和 Western blot 评估细胞凋亡。

结果

MS 治疗逆转了胆胰酶诱导的 AP 小鼠血清淀粉酶和脂肪酶水平的升高,减轻了胰腺的病理损伤,并降低了 TNFα、IL-6、IFNγ和 IL-10 的表达。此外,MS 处理的胰腺中 MPO 下调,SOD 上调,表明 MS 具有抗 AP 的抗氧化作用。此外,MS 可保护胰腺细胞免受胆胰酶诱导的凋亡,并消除 cleaved caspase-3。

结论

MS 对胆胰酶诱导的 AP 小鼠具有抗炎、抗氧化和抗凋亡作用,可能为胰腺炎的临床治疗提供一种有前途的治疗剂。

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