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卡托普利与甲泼尼龙在 L-精氨酸诱导的急性胰腺炎中的抗炎抗氧化作用比较。

Anti-inflammatory and Antioxidant Effects of Captopril Compared to Methylprednisolone in L-Arginine-Induced Acute Pancreatitis.

机构信息

Department of Biochemistry, Faculty of Pharmacy, Tanta University, El-Bahr Street, Tanta, El-Gharbia, 31527, Egypt.

出版信息

Dig Dis Sci. 2018 Jun;63(6):1497-1505. doi: 10.1007/s10620-018-5036-1. Epub 2018 Mar 29.

Abstract

BACKGROUND

Acute pancreatitis (AP) is an inflammatory disease mediated by damage in acinar cells and pancreatic inflammation with infiltration of leukocytes. The pancreatic renin-angiotensin system may play an important role in the pathogenesis of AP.

AIM

The present study aimed to investigate the possible protective role of captopril (CAP), an angiotensin-converting enzyme inhibitor, in attenuating L-arginine-induced AP rat model and to elucidate the underlying molecular mechanisms.

METHODS

Forty-eight adult male Wister rats were divided into four equal groups: control group (vehicle, orally for 10 days), AP group (3 g/kg L-arginine, single i.p.) on 10th day of the experiment, CAP group (50 mg/kg captopril, orally, once daily), and MP group (30 mg/kg methylprednisolone, orally, once daily). CAP and MP were administered for 10 days prior to L-arginine injection. Rats were sacrificed 24 h after arginine injection. Inflammatory biomarkers; tumor necrosis factor alpha (TNF-α) concentration, myeloperoxidase (MPO) activity, and inducible nitric oxide synthase (iNOS) gene expression were determined in pancreas. Oxidative stress biomarkers; pancreatic nitric oxide (NO) and reduced glutathione (GSH) concentrations were measured. Moreover, serum α-amylase and lipase activities were measured and histopathological studies of the pancreas were done.

RESULTS

CAP group showed a significant reduction in pancreatic TNF-α concentration, MPO activity, NO concentration, and downregulation of iNOS gene expression compared to AP group. CAP group also showed a significant increase in GSH concentration with amelioration of histological changes of AP as well as MP group.

CONCLUSION

Captopril treatment showed a protective and comparable effect with MP treatment in AP rat model.

摘要

背景

急性胰腺炎(AP)是一种由腺泡细胞损伤和白细胞浸润引起的炎症性疾病。胰腺肾素-血管紧张素系统可能在 AP 的发病机制中起重要作用。

目的

本研究旨在探讨血管紧张素转换酶抑制剂卡托普利(CAP)在减轻 L-精氨酸诱导的 AP 大鼠模型中的可能保护作用,并阐明其潜在的分子机制。

方法

将 48 只成年雄性 Wister 大鼠随机分为四组:对照组(载体,口服 10 天)、AP 组(第 10 天腹腔注射 3 g/kg L-精氨酸)、CAP 组(50 mg/kg 卡托普利,口服,每天一次)和 MP 组(30 mg/kg 甲泼尼龙,口服,每天一次)。在精氨酸注射前 10 天给予 CAP 和 MP 治疗。在精氨酸注射后 24 小时处死大鼠。测定胰腺中炎症生物标志物;肿瘤坏死因子-α(TNF-α)浓度、髓过氧化物酶(MPO)活性和诱导型一氧化氮合酶(iNOS)基因表达。测定氧化应激生物标志物;胰腺一氧化氮(NO)和还原型谷胱甘肽(GSH)浓度。此外,还测定了血清α-淀粉酶和脂肪酶活性,并对胰腺进行了组织病理学研究。

结果

与 AP 组相比,CAP 组胰腺 TNF-α浓度、MPO 活性、NO 浓度降低,iNOS 基因表达下调。CAP 组还显示 GSH 浓度显著升高,改善了 AP 的组织学变化,与 MP 组相当。

结论

CAP 治疗在 AP 大鼠模型中显示出与 MP 治疗相当的保护作用。

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