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Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Clodronate-superparamagnetic iron oxide-containing liposomes attenuate renal injury in rats with severe acute
Sheng-chun Dang1, Yan-hua Zeng, Ping-jiang Wang
1Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
Background And Objective:
It has been shown that macrophages play an important role in the development of severe acute pancreatitis (SAP), and eventually lead to multiple organ failure (MOF). Clodronate-liposome selectively depleted macrophages. This study was to investigate the role of renal macrophage infiltration in acute renal injury in rats with SAP and to evaluate the potential of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for diagnosis.
Methods:
Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-liposomes and SPIO-clodronate-liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate into the subcapsular space of rat pancreas. Sprague-Dawley rats were randomly divided into a control group, SAP plus SPIO-liposome (P) group, and SAP plus SPIO-clodronate-containing liposome (T) group. Kidney injury was evaluated by T2-weighted MRI scan. The levels of serum amylase (SAM), blood urea nitrogen (BUN), and serum creatinine (SCr) were measured by an automated enzymatic method. Serum tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in the pancreas and kidney were observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was detected with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In addition, the macrophage markers (CD68) of the renal tissue were detected with immunohistochemistry.
Results:
The pathological changes in the pancreas and kidneys of rats in the T group were milder than those in the P group. The MRI signal intensity of the kidneys in the P and T groups was significantly lower than that in the control group. There were significant changes in the two experimental groups (P<0.01). The levels of SAM, Bun, SCr, and TNF-α in rats in the P group were higher than those in the control group (P<0.01) and in the T group (P<0.01). The apoptosis of the kidney in the T group was higher than that in the P group at 2 and 6 h (P<0.01).
Conclusions:
Clodronate-containing liposomes protected against renal injury in SAP rats, and SPIO can be used as a tracer for MRI examination to detect renal injury in SAP rats. SPIO-aided MRI provided an efficient non-invasive way to monitor the migration of macrophages after renal injury in rats with SAP.
Insights
Clodronate liposomes reduced kidney injury in severe acute pancreatitis (SAP) rats by depleting macrophages. Superparamagnetic iron oxide (SPIO)-enhanced MRI effectively detected this renal injury and macrophage migration.
Area of Science:
- Biomedical Imaging
- Renal Pathophysiology
- Immunology
Background:
- Macrophages are implicated in severe acute pancreatitis (SAP) pathogenesis and multiple organ failure (MOF).
- Renal macrophage infiltration contributes to acute kidney injury (AKI) in SAP.
- Targeted macrophage depletion may mitigate SAP-induced AKI.
Purpose of the Study:
- Investigate the role of renal macrophage infiltration in SAP-induced AKI in rats.
- Evaluate superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) for diagnosing renal injury in SAP.
- Assess the therapeutic effect of macrophage depletion on SAP-related renal damage.
Main Methods:
- SAP models were induced in rats using sodium taurocholate injection.
- Rats were treated with SPIO-liposomes or SPIO-clodronate-liposomes to selectively deplete macrophages.
- Kidney injury was assessed via T2-weighted MRI, serum biomarkers (BUN, SCr), and histopathology (H&E, TUNEL, CD68 immunohistochemistry).
Main Results:
- Clodronate-liposome treatment significantly reduced pancreatic and renal pathological damage compared to control SPIO-liposomes.
- SPIO-enhanced MRI showed significantly lower kidney signal intensity in SAP groups, indicating injury.
- Serum markers of kidney injury and inflammation (TNF-α) were elevated in SAP rats but reduced by clodronate treatment.
Conclusions:
- Clodronate-containing liposomes offer protection against renal injury in SAP rats.
- SPIO-enhanced MRI serves as an effective non-invasive tool for detecting renal injury in SAP.
- SPIO-aided MRI facilitates monitoring of macrophage migration in SAP-induced renal injury.
Related Concept Videos
01:21Acute Pancreatitis II: Pathophysiology
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention