PI3K/AKt/mTOR Signaling Pathway Involved In The Regulation Of The Expression Of Hypoxia Inducible Factor-1A In Rats With Acute Pancreatitis

Objective : To observe PI3K/AKt/mTOR signaling pathwany regulate the expression of hypoxia inducible factor-1αin rats with acute pancreatitis. Methods: Fifty-six male SD rats were randomly divided into seven groups as blank control group(n=8), sham operation group(n=8), acute pancreatitis(AP) group (n=8), wortmannin pretreatment group (n=8), rapamycin pretreatment group (n=8) , wortmannin+rapamycin pretreatment group(n=8)and the solvent of DMSO/PBS control group(n=8). The rat model with AP was made by injection with 5% sodium deoxycholate through retrogradely bilio pancreatic ducts. For the pretreatment groups of wortmannin pretreatment, rapamiycin pretreatment and wortmannin+rapamycin were given intraperitoneal injection with the reagents of wortmannin, rapamiycin and wortmannin+rapamycin respectively prior to the AP model made, the solvent control group only given the DMSO/PBS solution,and rats in the sham group just only given operation procedure. The head of pancrease in rats were harvested at 6 hours after the model set up, the expression of HIF-1αmRNA were detected by RT-PCR, the expression of HIF-1α, Akt, p-Akt, p70S6K and p-p70S6K proteins were detected by western blot respectively in pancreatic tissues. Results: The expression of HIF-1αmRNA in the head of pancrease in rats were seldom both in the blank control group and the sham operation control group, and there was no significant difference between these two groups(P>0.05). The expression of HIF-lαmRNA were significantly higher in the AP group, wortmannin group, rapamycin group, wortmannin+rapamycin group and solvent control group than that in the blank control group(P<0.01), and there was no significant difference between the pretreatment groups and the AP group(P>0.05). The expression of Akt,p-p70s6k proteins were stable,and there was no significant difference in groups(P>0.05). The expression of HIF-lα, p-Akt, p-p70s6k proteins were seldom both in the blank control group and the sham operation control group, and there was no significant difference between these two groups(P>0.05). The expression of HIF-1α, p-Akt, p-p70s6k proteins were significantly higher in the AP group than that in the blank control group(P<0.01). In the pretreatment groups of wortmannin, rapamycin and wortmannin+ rapamycin,the expression of HIF-1α,p-p70s6k protein were significantly decreased compared to that in the AP group(P<0.01), but they were still significantly higher than that in the blank control group(P<0.01),and there was no difference between the solvent control group and the AP group(P>0.05). Conclusion:The expression of HIF-1αmRNA and protein in head of pancrease in rats with AP were increased significantly, wortmannin and rapamycin, PI3K/Akt/mTOR signaling pathway inhibitors, reduced the expression of HIF-1αmRNA and protein significantly in rats with acute pancreatitis, these results indicated that the PI3K/Akt/mTOR signaling pathway involved the regulation of the expression of HIF-1α,and suggest that PI3K/Akt/mTOR signaling pathway maybe a potential target for prevent and treatment of acute pancreatitis.