Experimental Acute Pancreatitis Models: History, Current Status, and Role in Translational Research

Abstract

Acute pancreatitis is a potentially severe inflammatory disease that may be associated with a substantial morbidity and mortality. Currently there is no specific treatment for the disease, which indicates an ongoing demand for research into its pathogenesis and development of new therapeutic strategies. Due to the unpredictable course of acute pancreatitis and relatively concealed anatomical site in the retro-peritoneum, research on the human pancreas remains challenging. As a result, for over the last 100 years studies on the pathogenesis of this disease have heavily relied on animal models. This review aims to summarize different animal models of acute pancreatitis from the past to present and discuss their main characteristics and applications. It identifies key studies that have enhanced our current understanding of the pathogenesis of acute pancreatitis and highlights the instrumental role of animal models in translational research for developing novel therapies.

Ketogenesis acts as an endogenous protective programme to restrain inflammatory macrophage activation during acute pancreatitis

“…To further confirm the role of dietary ketone body in the prevention of AP, the CER/LPS-SAP model mimicking septic necrotising AP was employed. 31 Similarly, 1,3-butanediol pretreatment was able to reduce the overall pancreas histopathology score ( Figure 4 e), lung alveolar membrane thickening ( Figure 4 f) and the TNFα levels of monocytes/macrophages in the pancreas, spleen, and mesenteric lymph nodes ( Figure 4 g).

Figure 4 Exogenous supplementation with βOHB alleviates the severity of AP, (a–d) Mice were pre-fed with or without the precursor of βOHB, 1,3-butanediol , in drinking water for 1 week prior to AP induction (n = 4-6 / group).

…”

“…Mouse models included ( 1 ) hourly intraperitoneal injections of 50 or 100 μg/kg caerulein (Yeasen Biotech) dissolved in normal saline for 7 times to induce necrotising AP (CER-AP [Cer*7]) without marked systemic inflammation 29 ; ( 2 ) hourly intraperitoneal injections of 100 μg/kg caerulein 12 times to induce more severe necrotising AP (CER-AP [Cer*12]) with overt lung and liver injuries 29 , 30 ; ( 3 ) and LPS (10 mg/kg; Sigma Aldrich) superimposed on a Cer*7 regimen right after the last injection of caerulein to induce necrotising SAP (CER/LPS-SAP) mimicking septic conditions with multiple organ failure. 31 Control mice received saline injections following the respective regimens. All animals were sacrificed at 24 h after first caerulein or saline injection unless otherwise mentioned.…”

Current therapeutic approaches to haemostasis correction in covid-19: a systematic review

“…Что касается инфильтрации воспалительных клеток при COVID-19 [4,26], гепарин может напрямую взаимодействовать с эндотелиальными клетками сосудов, что приводит к снижению рекрутинга нейтрофилов и прямому ингибированию их активации [22]. Доказано, что гепарин и его производные ослабляют воспаление и в других моделях, характеризующихся сильным иммунным ответом, включая панкреатит [27] и сепсис [28]. Клиническое использование гепарина в качестве противовоспалительного агента продемонстрировало его ограниченную эффективность при заболеваниях человека, включая воспалительные заболевания кишечника, астму, реактивное заболевание дыхательных путей и острый коронарный синдром [22,29].…”

Reduction in O-GlcNAcylation Mitigates the Severity of Inflammatory Response in Cerulein-Induced Acute Pancreatitis in a Mouse Model

“…In the current study, we aimed to determine if a pancreas-specific transgenic reduction in OGT in an in vivo mouse model affects the severity of cerulein-induced AP [25]. Our findings suggest that the partial loss of OGT in pancreatic tissue reduces the severity of AP induced by cerulein, highlighting OGT as a potential molecular target to ameliorate AP in patients.…”