Published online Feb 14, 2019. doi: 10.3748/wjg.v25.i6.683
Peer-review started: November 14, 2018
First decision: December 28, 2018
Revised: January 10, 2019
Accepted: January 20, 2019
Article in press: January 21, 2019
Published online: February 14, 2019
Obesity has contributed to the increased incidence and severity of acute pancreatitis (AP), specifically by increasing the risk of multisystem organ failure. However, the mechanism by which obesity influences AP has not been elucidated to date. There is no effective strategy for preventing AP from causing organ deterioration in obesity; thus, the current management standard is supportive and symptomatic. Therefore, investigations of how obesity may contribute to aggravating inflammatory organ injury in AP and identification of potential treatments are urgently required.
Our previous studies have demonstrated that high-fat diet-induced obesity can cause extensive inflammatory damage, especially multiple-organ inflammatory injury, in rats. However, the effect of high-fat diet-induced obesity on AP is still unknown. Sheng-jiang powder (SJP) is considered able to ameliorate the inflammatory response and histopathological lesions in multiple organs in obese rats. Could SJP alleviate multiple-organ inflammatory injury in AP by preventing obesity in rats? Therefore, this study aimed to explore the mechanisms of the effect of high-fat diet-induced obesity on inflammatory organ injury in AP rats and observe the effect of SJP on multiple-organ inflammatory injury in AP in rats fed a high-fat diet to provide an experimental basis for its clinical application in the future.
To explore how high-fat diet-induced obesity may contribute to aggravating inflammatory organ injury in AP rats and observe the effect of SJP on multiple-organ inflammatory injury in AP in rats fed a high-fat diet.
In this study, an obese rat model was induced by high-fat diet feeding, which is widely accepted and used for the induction of obesity in rats. The AP rat model was induced by a retrograde injection of sodium taurocholate into the biliopancreatic ducts, which is widely used to induce AP in rats. The levels of serum biochemistry parameters [triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and amylase] were measured using an HITACHI automatic biochemical analyzer (7170A, HITACHI, Tokyo, Japan). The levels of serum inflammatory cytokines (IL-6 and IL-10) and tissue oxidative stress cytokines [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), and myeloperoxidase (MPO)] were measured by ELISA, which is a simple, rapid, accurate, and sensitive method. All histopathological sections were observed and scored by two independent blinded pathologists using different scoring systems specific to different tissues.
Statistical analyses were performed with GraphPad Prism 6.01 software. All data are expressed as the mean ± standard deviation and passed the normality test. Two-sided one-way analysis of variance (followed by multiple pairwise comparisons using the Dunnett-t test) or the Kruskal-Wallis test was used to discover the differences among the three groups. In addition, Student’s t-test was used to compare the difference in the amylase levels between the control group (CG) and CG’ (CG before AP induction).
In the present study, serum triglyceride, total cholesterol, interleukin (IL)-6, and IL-10 levels in the obese AP rats were extremely high, and serum HDL-c level was significantly low. Enhanced oxidative damage was observed in the pancreas, heart, spleen, lung, intestine, liver, and kidney. Additionally, an imbalance in the antioxidant defense system, especially in the pancreas, spleen, intestine, and liver, was observed in the obese AP rats. Interestingly, SJP significantly increased serum HDL-c and IL-10 levels, decreased serum triglyceride and total cholesterol levels, induced oxidative stress in multiple organs, and ultimately ameliorated the pathological damage to the liver.
The preventive effect of SJP on AP in obesity remains to be determined. Moreover, this study provides partial information about multiple-organ injuries in obese AP rats, but the more specific mechanism needs further study. Finally, the specific effective monomer components and tissue pharmacokinetics of SJP should be considered to provide more systematic and comprehensive evidence for the clinical application of this Chinese decoction.
This study demonstrates that high-fat diet-induced obesity may aggravate the inflammatory reaction and pathological injury to multiple organs, especially leading to a strong and extensive oxidative stress response in organs, in sodium taurocholate-induced AP rats. In addition, SJP may alleviate multiple-organ inflammatory injury in AP in rats fed a high-fat diet.
As we observed that SJP may ameliorate multiple-organ inflammatory injury in AP in rats fed a high-fat diet by regulating the oxidative stress response, further investigation of the underlying molecular mechanism is urgently required to provide experimental evidence for wider clinical usage.