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局部胰腺肾素-血管紧张素系统对重症急性胰腺炎大鼠微循环的影响

Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis.

作者信息

Pan Zhijian, Feng Ling, Long Haocheng, Wang Hui, Feng Jiarui, Chen Feixiang

机构信息

Department of Gastroenterology Surgery, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science & Technology, Wuhan 430014, Hubei, China.

Department of gynecology and obstetrics, Fifth Hospital of Wuhan, Wuhan 430050, Hubei, China.

出版信息

Korean J Physiol Pharmacol. 2015 Jul;19(4):299-307. doi: 10.4196/kjpp.2015.19.4.299. Epub 2015 Jun 30.

Abstract

Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.

摘要

重症急性胰腺炎(SAP)通常与多器官功能障碍和局部并发症相关。研究发现,在药物诱导的SAP中,胰腺局部肾素-血管紧张素系统(RAS)显著上调。本研究旨在探讨血管紧张素II受体抑制剂缬沙坦对大鼠模型中SAP时RAS双重作用的影响,并阐明其潜在机制。将3.8%牛磺胆酸钠(1 ml/kg)注射到胰腺被膜以诱导胰腺炎。假手术组大鼠在相同部位注射生理盐水。我们还通过测定血清淀粉酶、脂肪酶和髓过氧化物酶的活性、组织学和生化分析、放射免疫测定、荧光定量PCR和蛋白质印迹分析,研究实验性诱导的SAP对胰腺局部RAS表达的调节。结果表明,缬沙坦可通过抑制微循环障碍和炎症有效抑制局部RAS,从而预防实验性急性胰腺炎。结果提示,胰腺RAS在胰腺功能调节中起关键作用,并显示出作为AT1受体拮抗剂的应用潜力。此外,其他RAS抑制剂可能成为急性胰腺炎的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc4e/4499641/6d472cb2934d/kjpp-19-299-g001.jpg

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