| Objective To investigate the influence of interleukin 10 (IL-10) on IL-6 and tumour necrosis factorα(TNF-α), serum calcium, intercellular adhesion molecule 1 (ICAM-1) and parathyroid hormone receptor 1 (PTHR1) gene expression in kidney and bone tissue in rats with severe acute pancreatitis (SAP), and to explore the the mechanism of hypocalcemia and the role of IL-10 in SAP.Methods 54 male SD rats were divided randomly into three groups: sham operation group (SO), SAP group, SAP plus IL-10 treatment group (IL-10). SAP model was made by injecting 5% sodium deoxycholate into pancreatic-biliary duct. Serum total calcium, ionized calcium, amylase, volume of ascites and histological change of pancreas were determined at 12, 24h after induction of SAP. Serum TNF-αand IL-6 were detected by ELISA. The rat kidney and bone tissue were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for PTHR1 and ICAM-1 mRNA expression, by Western-blot for PTHR1 protein expression.Results(1) The elevated serum amylase, considerable ascites and significant necrosis and hemorrhage were observed after SAP onset. As compared with SAP group, the ascites got significantly decreased, the pancreatic pathological change attenuated, and the survival rate improved in IL-10 group.(2) Serum TNF-αand IL-6 levels of SAP group got significantly increased, the ICAM-1 mRNA expression in bone and kidney up-regulated and the concentration of serum total calcium and ionized calcium reduced, especially 12h after SAP onset. (3) In IL-10 treatment group, the levels of serum TNF-αat 24h [(13.2±6.1)pg/ml vs. (24.5±11.8)pg/ml; t=2.379,P=0.033] and IL-6 at 12h [(30.8±17.7)pg/ml vs. (121.4±39.1)pg/ml; t=5.651,P=0.000] and 24h [(15.9±6.6)pg/ml vs. (51.5±14.7)pg/ml; t=5.909,P=0.000] got remarkably decreased; the ICAM-1 mRNA expression in bone and kidney downregulated; the serum total calcium levels at 12h [(2.17±0.07)mmol/L vs. (2.02±0.06)mmol/L,P=0.002] and 24h [(2.21±0.10)mmol/L vs (2.11±0.08)mmol/L, P=0.032] and the ionized calcium levels at 12h [(1.11±0.05)mmol/L vs (1.01±0.06)mmol/L, P=0.001] and 24h [(1.17±0.06)mmol/L vs (1.09±0.08)mmol/L, P=0.014] alleviated, compared with SAP group. The levels of serum TNF-αand IL-6 had a negative correlation to the concentration of serum total calcium.(4) The expression of PTHR1 protein and mRNA in the rat kidney and bone were decreased(P<0.01). As compared with SAP group, the expression of PTHR1 protein and mRNA elevated (P<0.01) in IL-10 group. The levels of serum IL-6 had a negative correlation to the PTHR1 protein expression of kidney (r=-0.613,P=000) and bone tissue (r=-0.564,P=001). The levels of serum TNF-αhad also a negative correlation to the PTHR1 protein expression of kidney (r=-0.610,P=000) and bone tissue (r=-0.659,P=000).Conclusion(1) It is a better SAP treatment model induced by pancreatic-biliary duct retrograde injection plus left femoral vein cannulation.(2) The decreased expression of PTHR1 in kidney and bone is one of the vital causes of hypocalcemia in SAP.(3)The excessive release of inflammatory cytokine is the foundation of PTHR1 low level expression which can cause PTH resistance and hypocalcemia in SAP.(4)The use of IL-10 in SAP can inhibit the release of inflammatory cytokines, up-regulate the expression of PTHR1 and increase serum calcium.
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