Expression of glycogen synthase kinase-3β in renal damage of acute necrotizing pancreatitis and its mechanism

Objective To observe the changes of tissue morphology and ultrastructure of kidney in the rat model of acute necrotizing pancreatitis (ANP), and to investigate the protein expression of glycogen synthase kinase-3β(GSK-3β) and phosphorylated GSK-3βin renal tissue. Methods Sixty SPF male SD rats were randomly divided into 5 groups (n=12 for each group) according to random number method, including control group, ANP 3 h, 6 h, 12 h, 24 h groups. ANP model was established by retrograde infusion of 5% sodium taurocholate solution into the biliopancreatic duct. Rats were sacrificed at corresponding time points to collect pancreatic and left renal tissue. Serum amylase (AMY), lipase (LIPA), creatinine (Cr) and urea nitrogen (BUN) levels were detected. Pancreatic and renal tissues were routinely pathologically examined.Rephrocytes′ ultrastructure changes were observed by projection electron microscope. GSK-3β protein expression and phosphorylated GSK-3β(p-GSK-3β) in kidney tissue were quantified by Western-blot. Results Serum AMY, LIPA, Cr, Bun and pathological scores for pancreatic and renal tissues in ANP groups were obviously higher than those in control group, which increased gradually with the progress of pancreatitis. In ANP rats, it was observed that the microvilli on the surface of the epithelial cells of renal tubules were swelling and irregularly arranged, the nucleus was condensed and broken, the nuclear chromatin was condensed and separated from the nuclear membrane, the mitochondria was condensed, swelling and vacuolated. The expression levels of GSK-3β protein in the renal tissue of the control group and ANP 3 h, 6 h, 12 h, 24 h groups were 0.702±0.044, 0.876±0.017, 0.872±0.034, 0.855±0.035 and 0.852±0.032, respectively. The expression levels of p-GSK-3β were 0.626±0.029, 0.790±0.029, 0.616±0.021, 0.448±0.028 and 0.439±0.017. GSK-3β protein expression was higher in ANP group than in control group, and the difference was statistically significant (all P<0.05). But there was no statistically significant difference at different time points in ANP group. p-GSK-3β protein expression increased at 3 h after modeling, and then gradually decreased. p-GSK-3β protein expression was higher in ANP 3 h group than control group and other ANP groups, which in ANP 12 h, 24 h group was obviously lower than control group and ANP 3 h, 6 h group, and the difference was statistically significant (P<0.05). Conclusions GSK-3β expression in the kidney of ANP rats began to increase at 3 h after modeling and maintain a high level. p-GSK-3β was transiently increased at 3 h after modeling and then gradually decreased to a level obviously lower than control group. It indicated that these changes may play a crucial role in ANP associated kidney injury. Key words: Pancreatitis, acute necrotizing; Acute kidney injury; Glycogen synthase kinase-3β