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Updated: Jul 4, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Alteration of Mrp2 and P-gp expression, including expression in remote organs, after intestinal ischemia-reperfusion
Jiro Ogura1, Masaki Kobayashi, Shirou Itagaki
1Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
Abstract:
The present study was carried out in order to identify the changes in expression of multidrug resistance-associated protein (Mrp) 2 and P-glycoprotein (P-gp) in the intestine and remote organs after intestinal ischemia-reperfusion (I/R). Mrp2 expression in the jejunum and liver was decreased at 6 h after I/R. This decrease in Mrp2 expression was associated with an increase in the serum level of IL-6. These results suggest that the decreased Mrp2 expression after intestinal I/R was regulated by IL-6. The expression level of mdr1a in the ileum, which encodes P-gp, was decreased at 6 and 24 h after I/R, and the expression level of mdr1b, also encodes P-gp, was not altered at any time. P-gp protein expression in the ileum was decreased at 6 h after I/R. In the liver, mdr1a expression was decreased at 6 h after I/R, but mdr1b expression was increased at 6 h after I/R. P-gp protein was not altered at any time. In the kidney, mdr1a expression was decreased at 24 h after I/R, but mdr1b expression was not altered at any time. P-gp protein expression in the kidney was decreased at 24 h after I/R, as was mdr1a expression. These results suggest that P-gp expression after intestinal I/R differs in each organ. This is the first report to provide evidence that expression levels of transporters in remote organs are altered intestinal after I/R.
Insights
Intestinal ischemia-reperfusion (I/R) decreases multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein (P-gp) expression in the intestine and remote organs. IL-6 may regulate decreased Mrp2 expression following I/R.
Area of Science:
- Physiology
- Biochemistry
- Molecular Biology
Background:
- Intestinal ischemia-reperfusion (I/R) is a critical condition affecting gut integrity and systemic function.
- Multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein (P-gp) are key efflux transporters crucial for xenobiotic and metabolite elimination.
- Understanding transporter expression changes post-I/R is vital for predicting drug efficacy and toxicity.
Purpose of the Study:
- To investigate alterations in Mrp2 and P-gp expression in the intestine and distant organs following intestinal I/R.
- To explore the potential role of Interleukin-6 (IL-6) in regulating Mrp2 expression after I/R.
Main Methods:
- Intestinal I/R model established in a preclinical setting.
- Quantitative analysis of Mrp2 and P-gp mRNA (mdr1a, mdr1b) and protein expression levels.
- Measurement of serum IL-6 levels.
Main Results:
- Mrp2 expression decreased in the jejunum and liver 6 hours post-I/R, correlating with increased serum IL-6.
- Ileal P-gp (mdr1a) expression decreased at 6 and 24 hours post-I/R, with reduced protein levels at 6 hours.
- Remote organs (liver, kidney) exhibited differential changes in P-gp expression (mdr1a and mdr1b) following intestinal I/R.
Conclusions:
- Intestinal I/R significantly alters the expression of Mrp2 and P-gp in both the intestine and remote organs.
- IL-6 is implicated as a regulator of Mrp2 expression following intestinal I/R.
- This study provides the first evidence of altered transporter expression in remote organs after intestinal I/R, highlighting potential systemic consequences.
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