Department of Biochemistry, Faculty of Pharmacy, Tanta University, El-Bahr Street, Tanta, El-Gharbia, 31527, Egypt.
Dig Dis Sci. 2018 Jun;63(6):1497-1505. doi: 10.1007/s10620-018-5036-1. Epub 2018 Mar 29.
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.
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.
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.
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.
Captopril treatment showed a protective and comparable effect with MP treatment in AP rat model.
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。
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。
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。
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。
CAP 治疗在 AP 大鼠模型中显示出与 MP 治疗相当的保护作用。
