Role of PI3K/Akt signaling in the protective effect of magnesium sulfate against ischemia-perfusion injury of small intestine in rats.
BACKGROUND
The protective effects of magnesium sulfate against ischemia-reperfusion injury of the small intestine in Sprague-Dawley (SD) rats have been confirmed in our previous research. However, its exact mechanism is unclear. This study was to evaluate the role of PI3K/Akt signal pathway in the protective effect of magnesium sulfate against ischemia-reperfusion injury of the small intestine in SD rats.


METHODS
Rat model of intestinal ischemia-reperfusion injury was used. The SD rats were divided into four groups randomly: sham operation group, ischemia-reperfusion group, magnesium sulfate group and magnesium sulfate plus LY294002 (an inhibitor of PI3K) group. The pathological changes of intestinal mucosa were examined; the activity of diamine oxidase (DAO) in plasma, the plasma contents of malondialdehyde (MDA), and apoptosis rate of the intestinal mucosal cells were determined and compared. The expression of p-Akt was detected by Western blotting.


RESULTS
There were more evident pathological changes of the intestinal mucosa (higher Chiu's score, P < 0.05), enhanced DAO activity (P < 0.05), elevated contents of MDA (P < 0.05), higher apoptosis rate (P < 0.05), and lower level of p-Akt (P < 0.05) in the ischemia-reperfusion group compared with the sham operation group. There were less evident pathological changes of the intestinal mucosa (lower Chiu's score, P < 0.05), lower DAO activity (P < 0.05), lower contents of MDA (P < 0.05), and lower apoptosis rate (P < 0.05), but higher level of p-Akt (P < 0.05) in the magnesium sulfate group compared with the ischemia-reperfusion group. There were more evident pathological changes of the intestinal mucosa (higher Chiu's score, P < 0.05), higher contents of MDA (P < 0.05), higher DAO activity (P < 0.05) and higher apoptosis rate (P < 0.05), and lower level of p-Akt (P < 0.05) in the magnesium sulfate plus LY294002 group compared with the magnesium sulfate group.


CONCLUSIONS
Activation of PI3K/Akt signal pathway results in the reduction of cell apoptosis, which likely accounts for the protective effect of magnesium sulfate against intestinal ischemia-reperfusion injury.
Chen
Shi-da
SD
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Chen
Ya-bin
YB
Peng
You
Y
Xu
Jia
J
Chen
Su-shan
SS
Zhang
Jun-long
JL
Li
Zheng-zhang
ZZ
Tan
Zhi
Z
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects*; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D008315:Malondialdehyde / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*
D008315:Malondialdehyde; D008278:Magnesium Sulfate; D006631:Amine Oxidase (Copper-Containing); D051057:Proto-Oncogene Proteins c-akt