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吸入富氢气体可预防雨蛙肽诱导的小鼠急性胰腺炎,同时增强胰腺 HSP60 蛋白表达。

Pre-inhalation of hydrogen-rich gases protect against caerulein-induced mouse acute pancreatitis while enhance the pancreatic Hsp60 protein expression.

机构信息

Department of Pathophysiology, Tongji University School of Medicine, 1239 Siping Road, Shanghai, 200092, China.

Shanghai Asclepius Meditec Co. Ltd., 758 Jiaxin Road, Shanghai, 201818, China.

出版信息

BMC Gastroenterol. 2021 Apr 19;21(1):178. doi: 10.1186/s12876-021-01640-9.

Abstract

BACKGROUND

Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. Aim of this study was to investigate effect of hydrogen pretreatment on AP and the mechanisms, focusing on pancreatic oxidative stress and Hsp60 expression.

METHODS

80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1 h, 3 h and 5 h (n = 6-8). Mouse AP model was induced by intraperitoneal injection of 50 μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance.

RESULTS

The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1 h and 5 h.

CONCLUSIONS

Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

摘要

背景

急性胰腺炎(AP)缺乏有针对性的预防和治疗措施。AP 的发病机制仍有一些关键点尚未阐明,如胰腺酶的早期激活。最近的一些报道表明,氢气对几种 AP 动物模型具有保护作用,其机制与抗氧化活性有关。热休克蛋白 60(Hsp60)已知伴随胰腺腺泡细胞中胰腺酶的合成和分泌途径,而 Hsp60 在 AP 中的作用仍然是一个研究课题。本研究旨在探讨氢气预处理对 AP 及机制的影响,重点关注胰腺氧化应激和 Hsp60 表达。

方法

将 80 只小鼠随机分为 4 组:HAP 组、AP 组、HNS 组和 NS 组,每组均设置 3 个观察时间点:1 h、3 h 和 5 h(n=6-8)。AP 组和 HAP 组小鼠腹腔注射 50 μg/kg 蛙皮素,每小时 1 次,共 6 次,诱导 AP 模型;NS 组和 HNS 组小鼠以相同方式给予生理盐水(NS)注射作为对照。HAP 组和 HNS 组小鼠在首次注射蛙皮素或 NS 前 3 天进行富氢气体吸入治疗,而 AP 组和 NS 组小鼠在正常空气条件下进行。观察胰腺组织病理学、血浆淀粉酶和脂肪酶、血浆白细胞介素-1(IL-1)和白细胞介素-6(IL-6)、胰腺谷胱甘肽(GSH)和丙二醛(MDA)以及 Hsp60 mRNA 和蛋白表达的变化。采用单因素方差分析进行比较。

结果

富氢气体预处理明显改善了 AP 小鼠的胰腺病理变化、血浆淀粉酶和脂肪酶活性以及血浆 IL-1 和 IL-6 水平的升高,同时增加了胰腺 GSH 含量,降低了胰腺 MDA 含量。此外,富氢气体预处理改善了 AP 小鼠胰腺组织中 Hsp60 蛋白的表达。

结论

富氢气体吸入预处理对 AP 小鼠具有良好的保护作用,减轻氧化应激和早期胰腺 Hsp60 蛋白增加的可能机制值得关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/496c/8056676/55ea021a5071/12876_2021_1640_Fig1_HTML.jpg

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