The Study On The Role Of TREM-2 In Abdominal Sepsis

Objective: To investigate the correlation between the triggering receptor expressed on myeloid cells-2(TREM-2) and the janus kinase/signal transducer and activator of transcription(JAK/STAT) pathway in rats with abdominal sepsis.Methods: Adult male Wistar rats with weight 304±11g were selected in this study. The experimental design was divided into two parts: the first part was the establishment of the abdominal sepsis model. A total of 80 rats were randomly divided into normal control group(n=8)、sham-operated group(n=32)and CLP group(n=40). Abdominal sepsis model was produced by cecal ligation and puncture(CLP) in CLP group, rats in the normal control group had no special treatment, while those in sham-operated group were only received Anesthesia and the switch of abdominal cavity without surgery.The 72 hours mortality was recorded, and the concentration change of serum IL-1、IL-4、IL-6、IL-10 were detected by ELISA. The second part was to observe the expression of TREM-2 in hepatic tissue after being intervened by the application of AG490 and RPM. Rats were randomly divided into sham-operated group(n=24),CLP group(n=48),AG490 group(n=48) and rapamycin(RPM) group(n=48), Among them, rats in the third group were given AG490 8mg/kg before CLP, while those in the fourth group were given RPM 0.4mg/kg. The serum、 peritoneal drainage fluid and liver tissues of each group were collected at 6,24, 48, 72 hours after treatment. The concentration change of IL-1、IL-4、IL-6、IL-10 were detected by ELISA. The m RNA expressions of TREM-2 in the liver tissues were determined by RT-PCR.Results:The first part: There was no obvious change in normal control group and sham-operated group with the elapse of time.While 72 hpostoperative rats in CLP group were observed to have the change of the congestion and adhesion of viscera, markedly swollen ileum, increasing abdominal effusion and cacosmia. Compared with normal control group and sham-operated group, rats’ concentration of IL-1、IL-4、IL-6 、 IL-10 in CLP group was significantly increased.It demonstrated that the abdominal sepsis model was established successfully.The second part:(1) Compared with sham-operated group, the concentration of serum inflammatory factor were significantly increased, and reached the peak at 72 hours both in CLP group and in AG490 group. The concentration of serum IL-1、IL-4、IL-10 in RPM group was highest at 6 hour,then gradually declined,and was obviously lower than that of the CLP group at the same time point. The concentration of serum IL-6 had no difference at 6h, compared with that in CLP group. However, that was apparently decreased at 24 h, 48 h, 72 h.(2) Compared with sham-operated group, the levels of peritoneal drainage fluid inflammatory factor were significantly increased, and reached at the peak at 72 h both in CLP group and in AG490 group.There was no difference between CLP group and AG490 group. But the levels of peritoneal drainage fluid inflammatory factor in RPM group were highest at 6 hour and it showed a tendency of gradually decresing over time. Although the concentration of IL-1 and IL-6 of serum and peritoneal drainage fluid in RPM group at 6h is the same as that of CLP group, it is remarkablely decreased at 24 h, 48 h, and 72 h.(3) After being detected by RT-PCR, the m RNA expressions of TREM-2 of liver tissues in CLP group showed a gradually decreased tendency,and it was consistent with that of the AG490 group.While the RPM group’s expression of TREM-2 was significantly elevated at 24,48,72 hours.Conclusion:1、 The experiment confirmed that the expressions of TREM-2 of liver tissues in rats with abdominal sepsis was markedly decreased, while the levels of serum and peritoneal drainage fluid inflammatory factors was increased significantly. These data proved that TREM-2 could limit the extension of inflammatory response. The lack of TREM-2 lead to this restrictive effection was weaken and inflammatory factors were released largely, eventually sepsis was aggravated.2、 After the application of RPM, the expression of TREM-2 was significantly elevated, and the release of inflammatory factors was obviously reduced. It indicated that JAK/STAT pathway may block the expression of TREM-2, and inhibiting STAT can up-regulate the expression of TREM-2, so that TREM-2 can play the role of regulating the inflammatory reaction and immune response.Nevertheless, the specific mechanisms need a further investigation.