柚皮素通过 NLRP3 和 Nrf2/HO-1 通路保护两种实验性小鼠急性胰腺炎模型。

Naringenin Protects against Acute Pancreatitis in Two Experimental Models in Mice by NLRP3 and Nrf2/HO-1 Pathways.

机构信息

Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Clinical Medical College of Nanjing Medical University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China.

Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

出版信息

Mediators Inflamm. 2018 Apr 8;2018:3232491. doi: 10.1155/2018/3232491. eCollection 2018.

BACKGROUND

Naringenin (Nar) is a type of flavonoid and has been shown to have anti-inflammatory and antioxidative properties. However, the effects of Nar on acute pancreatitis (AP) have not been well studied. In this study, we aimed to investigate the function of Nar in a mouse model of AP.

METHODS

Mild acute pancreatitis (MAP) was induced by caerulein (Cae), and severe acute pancreatitis (SAP) was induced by L-arginine in mice. Nar was administered intraperitoneally at doses of 25, 50, or 100 mg/kg following MAP induction and at a dose of 100 mg/kg following SAP induction. The serum levels of cytokines, lipase, and amylase were determined, and pancreatic and pulmonary tissues were harvested.

RESULTS

The serum levels of amylase, lipase, and cytokines were significantly decreased in both MAP and SAP models after Nar treatment. The malondialdehyde (MDA) levels of the pancreatic tissue was significantly reduced in both MAP and SAP after Nar treatment. In contrast, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), total sulfhydryl (T-SH), and non-proteinsulthydryl (NP-SH) were markedly increased in both MAP and SAP after Nar treatment. The injury in pancreatic and pulmonary tissues was markedly improved as evidenced by the inhibited expression of myeloperoxidase, nod-like receptor protein 3, and interleukin 1 beta as well as the enhanced expression of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 in pancreatic tissues.

CONCLUSIONS

Nar exerted protective effects on Cae-induced MAP and L-arginine-induced SAP in mice, suggesting that Nar may be a potential therapeutic intervention for AP.

背景

柚皮素（Nar）是一种类黄酮，具有抗炎和抗氧化作用。然而，柚皮素对急性胰腺炎（AP）的影响尚未得到充分研究。在这项研究中，我们旨在研究 Nar 在小鼠 AP 模型中的作用。

方法

采用 caerulein（Cae）诱导轻度急性胰腺炎（MAP），采用 L-精氨酸诱导重症急性胰腺炎（SAP）。在 MAP 诱导后，给予 Nar 腹腔内注射 25、50 或 100mg/kg，在 SAP 诱导后给予 Nar 腹腔内注射 100mg/kg。测定血清细胞因子、脂肪酶和淀粉酶水平，并采集胰腺和肺组织。

结果

Nar 处理后，MAP 和 SAP 模型中血清淀粉酶、脂肪酶和细胞因子水平均显著降低。Nar 处理后，MAP 和 SAP 模型中胰腺组织丙二醛（MDA）水平显著降低。相反，MAP 和 SAP 模型中，Nar 处理后，谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）、谷胱甘肽 S-转移酶（GST）、总巯基（T-SH）和非蛋白巯基（NP-SH）均显著增加。MPO、NOD 样受体蛋白 3 和白细胞介素 1β的表达受到抑制，核因子红细胞 2 相关因子 2/血红素加氧酶-1 的表达增强，表明胰腺和肺组织损伤得到明显改善。