The Protective And Therapeutic Effects Of Insulin-like Growth Factor-1 On Inflammatory Injury In Rats With Severe Acute Pancreatitis

ObjectiveIn the early stage of severe acute pancreatitis(SAP),the mononuclear/macrophage system of the body is activated by a variety of injury factors,thereby releasing a large number of proinflammatory cytokines.A variety of proinflammatory cytokines such as interleukin-1?,interleukin-6(IL-1?,IL-6)and so on play a vital role in the development of SAP.A large number of studies have shown that p38 mitogen-activated protein kinase(p38MAPK)and nuclear factor-?B(NF-?B)signaling pathway have a very important role in the pathogenesis of SAP,The activation of intracellular signal transduction pathways such as p38MAPK,NF-?B is closely related to the production of proinflammatory cytokines.In the early work we found that p38MAPK,NF-?B signaling pathway in SAP can be activated,and produce a large number of proinflammatory cytokines to induce the body to produce inflammatory response.In recent years,insulin-like growth factor-1(IGF-1)has been paid more and more attention in the development of SAP.Studies have shown that IGF-1 has a protective effect on the lung injury and intestinal mucosal barrier damage of rats with SAP.The combination of growth hormone and somatostatin can significantly improve the prognosis of patients with SAP,but the specific mechanism is not clear.We will observe the therapeutic effect of IGF-1 on early onset of SAP rats,and study the expression of p38MAPK and NF-?B signal transduction pathway in pancreatic tissue and the expression of proinflammatory cytokines(IL-1?,IL-6)and the effect of IGF-1 on pancreatic histopathological score,and to investigate the role and mechanism of IGF-1 in the early stage of rats with SAP.Methods30 SD rats were randomized into the normal group,sham operation group,SAP group,high dose IGF-1 group and low dose IGF-1 group.The SAP model was established by the modified Aho method.Rats were sacrificed 6h after modeling for collection of pancreatic tissues,peripheral blood and ascites.The expression status of the serum cytokines(IL-1?,IL-6)was detected by enzyme-linked immuno sorbent assay(ELISA).Real-time PCR was used to detect the changes in MAPK p38 and NF-?B p65 mRNA transcription level in pancreatic tissues,and to have a histopathological examination of pancreatic tissue after routine HE staining.ResultsIn SAP rats,there were significant increases in ascites volume,transaminases,serum and ascites amylase,IL-1?and IL-6,compared to the normal control group and control group(P<0.05).IGF-1 intervention resulted in significant decreases in ascites volume,transaminases,serum and ascites amylase,IL-1 and IL-6,compared to the SAP group(P<0.05),and there were greater decreases in ascites volume,transaminases,serum and ascites amylase,IL-1 and IL-6 with increasing IGF-1 dose(P<0.05).ConclusionIGF-1 may act with p38MAPK,NF-?B signaling pathway,so that the activation of these two channels weakened,thus reduce the transcription and expression of proinflammatory cytokines such as IL-1?,IL-6,so the pathological damage of pancreatic tissue in rats is relieved,which effectively alleviates the condition of rats with SAP.