Abstract:Background and Aims: At present, in the research of hypertriglyceridemia acute pancreatitis (HTG-AP), the methods for generating animal models are diverse, and the models are also difficult to construct. Therefore, this study was conducted to develop a new method for establishing a rat HTG-AP model by using the hyperlipidemia inducing agent poloxamer-407 (P-407) combined with L-arginine.
Methods: Seventy-two male SD rats were equally randomized into normal control group, and low dose P-407
(0.12 g/kg), medium P-407 dose (0.25 g/kg) and high P-407 dose (0.50 g/kg) group. Rats in normal control group did not receive any treatment, and those in the other 3 groups underwent intraperitoneal injection of respective doses of P-407 once per day to induce hyperlipidemia. Six rats in each group were randomly selected on 1 week, 2 and 4 weeks later respectively, and underwent intraperitoneal injection of 20% L-arginine (2.5g/kg) twice (a 1-h time interval) to induce acute pancreatitis, and were sacrificed 24 h later, and then the blood samples were taken for measurement of the serum levels of liver and renal function parameters as well as the serum levels of triglyceride (TG), total cholesterol (TC), amylase (AMY) and lipase (LIPA), and the pancreatic tissues were harvested for observation and scoring of the pathological changes of pancreas.
Results: In each P-407 dose group compared with normal control group, the serum levels of liver and renal function parameters showed no significant changes at each time point (all P>0.05); the serum levels of TG and TC levels were significantly increased at each time point with a time- and dose-dependent manner (all P<0.05), in which, the TG level in low P-407 dose group did not reach a blood lipid standard of HTG-AP (TG>11.3 mmol/L) at each time point, while the TG level in high and medium P-407 dose group reached the blood lipid standard of HTG-AP from 1 week and 2 weeks after the experiment, respectively. In each P-407 dose group compared with normal control group, the serum levels AMY and LIPA were all significantly increased and the scores for pancreatic pathological injury were all significantly elevated, and all these effects presented a time- and dose-dependent manner (all P<0.05).
Conclusion: Using a suitable dose of P-407 (0.25-0.50 g/kg) combined with 20% L-arginine (2.5 g/kg) can successfully construct a stable rat HTG-AP model within a short period of time (1 week to 2 weeks). This model is easy to be replicated with good reproducibility, and can provide a convenient tool for studies in the relevant fields.