Role Of TREM-1 In The Regulation Of Gut Macrophages Phenotypic Trafficking In SAP Gut Impairment

Objective:To investigate the role of TREM-1 in the regulation of macrophage phenotype conversion in intestinal mucosal barrier injury of SAP.Method:72 SD rats were randomly divided into the Control group(n=8);sham operation group(Sham group);SAP group;SAP+ TREM-1 inhibitor group(LP17 group)and SAP+ NF-?B inhibitor group(PDTC group),the last four groups had 16 rats in each group,which were used for in vivo and in vitro experiments.The experimental rat model was established by intraperitoneal injection of cerulein combined with LPS.The pancreatic and intestine tissues were taken 6 hours after modeling and HE was performed on them.Elisa was used to measure the expression levels of TREM-1,IFN-?,iNOS,Arg-1 and IL-4 in peripheral blood.Intestinal macrophage was isolated,cultured and identified in vitro.qRT-PCR was used to detect the mRNA expression of TREM-1,iNOS,IFN-?,NF-?B,Arg-1,IL-4 and PPAR-? in rat intestinal macrophages.Western blotting was used to detect the expression of TREM-1,iNOS,Arg-1,NF-?B and PPAR-?.Result:Intraperitoneal injection of cerulein combined with LPS successfully established the rat model of SAP,the pancreas and pathological changes of the pancreas consistent with the performance of SAP.The results of HE showed that the pancreas and intestine tissues were severely damaged in SAP group compared with Control group and Sham group.The degree of pancreatic and intestinal tissue injury was significantly reduced in LP17 group and PDTC group compared with SAP group.Elisa results showed that the levels of TREM-1,IFN-? and i NOS in SAP group were significantly higher than those in Control group and Sham group(P<0.05)and the levels of Arg-1 were significantly lower(P< 0.05);the levels of IL-4 in SAP group rats were significantly lower than those in Control group(P<0.01);compared withSAP group,the expression levels of TREM-1,IFN-? and iNOS in LP17 group and PDTC group were significantly lower(P<0.05),IL-4 levels were much higher(P<0.05);the serum Arg-1 level in LP17 group was significantly higher than that in SAP group(P<0.05).The results of qRT-PCR showed that the changes of iNOS,IFN-?,Arg1 and IL-4 in rat intestinal macrophages were similar with the Elisa results.The level of TREM-1 in intestinal macrophages of SAP group was significantly higher than that of Control group and Sham group(P<0.01).The level of TREM-1 in LP17 group was significantly lower than that of SAP group(P<0.01).The level of TREM-1 in PDTC group was higher than that in Control group,Sham group and LP17 group(P<0.05).The expression of NF-?B in SAP group was higher than that in Control group and Sham group(P<0.01).The expression levels of NF-?B in LP17 group and PDTC group were obviously lower than those in SAP group(P<0.01).Compared with Control group and Sham group,the expression of PPAR-? in SAP group was much lower,and the expression levels of PPAR-? were much higher in LP17 group and PDTC group than in SAP group(P<0.01).The results of western blotting showed that the expression of TREM-1,iNOS and NF-?B in SAP group was significantly higher than that in Control group and(or)Sham group while the expression of PPAR-? and Arg-1 was significantly down-regulated(P<0.05).The expression of TREM-1,iNOS and NF-?B was down-regulated in LP17 group and PDTC group while the expression of PPAR-? and Arg-1 were up-regulated(P<0.05).Conclusions:The expression of TREM-1 in serum and intestinal tissue was increased in early stages of SAP.It may increase the expression of NF-?B,which is a key transcription factor of M1 macrophages,thereby regulating the conversion of intestinal macrophages to the M1 phenotype,which will strengthen the inflammatory response.And at the same time,the activation of PPAR-?(a key transcription factor of M2macrophages)was inhibited,resulting in the imbalance between M1 and M2 macrophages adn impairing the intestinal mucosal barrier function.If the expression of TREM-1 is promptly inhibited in early stages of SAP,the release ofpro-inflammatory cytokines associated with M1 macrophages can be effectively alleviated,and the damage of intestinal mucosa barrier function can be reduced.This provides a new approach for the treatment of intestinal mucosa barrier dysfunction and may improve the prognosis of patients with SAP.