Research Of The Pathogenesis Of The Severe Acute Pancreatitis And The Effects Of PDS On The Severe Acute Pancreatitis

The pathogenesis of severe acute pancreatitis (SAP) is still not completely clear now. Its onset process is hazardous with high mortality, the illness state evolves rapidly accompanied by multiple complications, which is extremely harmful. Although the modern medicine develops at very fast speed, the mortality hasn't been reduced till now.Therefore, a major of studies are processed on the pathogenesis of SAP. Taking together, these studies show that the imbalance of immune system plays an important role in the pathogenesis. Thus, the inhibition of cytokine/chemokine or proinflammatory cytokine overexpresstion could modulate the immune response, further, reduce the systemic inflammatory response and multiple organ failure, which have become a hot therapeutic measure now.Panaxadiol saponins (PDS) extracted from the panax. PDS could regulate intrinsic immune function. PDS can increase the immune ability of host cells normally. In contrast, PDS can inhibit the immune response if there is severe inflammatory reaction, in order to perform a protection of cells and organic functions. Thus, we made the study in this paper to investigate the inhibition of PDS on the immune response of SAP.1. The regulative effects of PDS on human peripheral blood monouclear cells (PBMC). Firstly, we used different concentration of PDS to induce the normal human PBMC in order to observe the regulative effect by detecting the levels of activated cytokine and cytokine/chemokine or proinflammatory cytokine in the serum of medium. Secondly, we administered LPS to made the LPS situmulating model group, Subsequently, the method was same with before.2. To investigate the pathogenesis on the murine SAP model from molecular level. Adult wistar rats were made SAP model as previous reports described. The cytokine/chemokine,proinflammatory cytokine,COX-2 and EGR-1 expresssion were evaluated by the level of their mRNA and secrete proteins at different time points.3. To evaluate the therapeutic effects of PDS, the rats were randomly divided into sham operation group, SAP model group, PDS treated group and Dexamethasone treated group and normal group. Then, we detected the inflammatory responses and the regulation for COX-2 and EGR-1 on the key time points by different concentration of PDS. The Dexamethasone treated group is positive comparison , the sham operation group and normal group were negative comparison.Result: The results showed that PDS had the bidirectional regulative effects for the normal PBMC. PDS in the concentration of 2～64 mg/L can activate PBMC and improve the expression of CD80,CD86 and HLA-DR. The increase is relative to the concentration of PDS. However, the activated ability and the expression of CD80,CD86 and HLA-DR decreased when the concentration added up to 128 mg/L and more dosage.LPS can activated PBMC and increased the expression of CD80,CD86 and HLA-DRLPS (P<0.01). The lower concentration of PDS can inhibit the molecule expression of activated human PBMC by LPS induced. The inhibition ability was relative with the concentration of PDS until to 64 mg/L. There was no discrimination between 128 mg/L and 256 mg/L for the inhibition ability. And the excretion of TNF-α,IL-6 and IL-10 was no meaning among different concentration groups(P>0.05).Serum TNF-αlevels in SAP model group were higher than that in the normal group and sham operation group at different time points(all P<0.01). There was no discrepancy between the normal group and sham operation group(P>0.05). The serum level of TNF-α,IL-6,IL-10 in the SAP model group increased with time(all P<0.01).The mRNA and secrere protein levels of COX-2 mRNA and EGR-1 mRNA in SAP model group were higher than that in the normal group and sham operation group at different time points(all P<0.01).The pathological changes in the normal group and sham operation group were less than those of SAP model group . The levels of AMY in the SAP model group was more than other groups(P<0.01). The levels of AMY in the low dose of PDS were higher than those in the normal group and sham operation group and Dexamethasone treated group(P<0.01). The levels of AMY in the moderate dose of PDS were higher than those in the normal group and sham operation group(P<0.01), but it was no difference in the high dose and Dexamethasone treated group. PDS and Dexamethasone can significant reduce the surum AMY levels.There can't detect the expression of COX-2 and EGR-1 in the normal group and sham operation group. The expression of COX-2 and EGR-1 in SAP model group and PDS and Dexamethasone treated group were obviously higher than those in the normal group and sham operation group(P<0.01) and relative with time, which decreased in the PDS and Dexamethasone treated groups.Conclusion: Although PDS can enhance the immune response of the host cells, it plays an inhibition effect on the PBMC activated by LPS, in order to protect the cell functions. The inhibition of PDS for inflammation reaction needs a prime concentration. There were obvious decrease for cytokine/chemokine,proinflammatory cytokine and the mRNA and secrete proteins of COX-2 and EGR-1 in the SAP model groups. Therefore, we suggest that PDS can play the therapeutic effects for SAP by decreasing the expression of EGR-1 and inhibiting the activation of proinflammatory cytokine.