The Effect Of Ginkgolide B On Expression Of Platelet Activating Factor Receptor In Pulmonary Tissues Of Rats With Severe Acute Pancreatitis And Its Mechanism

Objective: Wistar rats with severe acute pancreatitis (SAP) are complicated with acute lung injury (ALI) and treated with Ginkgolide B (BN52021), then by detecting the location and expression of platelet activating factor receptor (PAF-R) in pulmonary tissues, to elucidate the function of PAF-R in the pathogenesis, the effect of BN52021 on expression of PAF-R and its mechanism.Methods: 5% sodium taurocholate was retrogressively injected into the pancreatic duct system of rats to induce SAP. 180 male Wistar rats were randomly divided into three groups: SAP model group (SAP group, n=60), BN52021 treating group (BN group, n=60), and negative contrast group (NC group, n=60). Each group was divided into six timepoints (1h, 2h, 3h, 6h, 12h and 24h) according to the time course after finishing of animal model and each timepoint has 10 rats. After sacrificimg the rats at the respective timepoint, blood was collected to detect the levels of amylase and secretory phosphatidase A2(sPLA2), and pancreas and lungs were harvested to be stained using HE, observed and scored. Whether every rat with SAP was complicated with ALI was judged by its pulmonary pathlogical scoring. The location of PAF-R was detected by immunohistochemistry. The level of PAF-R mRNA and protein was detected by RT-PCR and Western blot separately.Results: (1) The level of amylase in plasma indicated: the level in SAP group and BN group both was significantly higher than that in NC group at all the same timepoints (p<0.05). The level in BN group was significantly lower than that in SAP group at all the same timepoints except 12h (p<0.05). The level of sPLA2 in plasma indicated: the level in SAP group was significantly higher than that in NC group at 6h, 12h and 24h (p<0.05). The level in BN group was significantly higher than that in NC group at 1h, 2h and 6h (p<0.05). The level in BN group was significantly higher than that in SAP group at 1h (p<0.05). (2) The pancreatic pathological change of SAP was observed in SAP group, while no pathological change was observed in NC group. The change and pathological score in BN group was significantly milder than that in SAP group. The pulmonary pathological change of ALI was observed in SAP group, while no pathological change was observed in NC group. The change and pathological score in BN group was significantly milder than that in SAP group. 84.9% of rats in SAP guoup and 74.5% of rats in BN guoup had ALI according to their pulmonary pathological scores. (3) Pulmonary bronchus epithelial cell expressed PAF-R. (4) The level of PAF-R mRNA in pulmonary tissues at 3h was higher than that at other timepoints in SAP group. The level in SAP group was significantly higher than that in NC group at 3h (p<0.05). The level of PAF-R mRNA at 6h was higher than that at other timepoints in BN group. The level in BN group was not significantly different with that in SAP group at all timepoints. The level in BN group was significantly higher than that in NC group at 3h (p<0.05). The level of PAF-R protein in pulmonary tissues at 12h was higher than that at other timepoints in SAP group. The level in SAP group was significantly higher than that in NC group at 1h (p<0.05). The level of PAF-R protein at 2h was higher than that at other timepoints in BN group. The level in BN group was not significantly different with that in SAP group at all timepoints. The level in BN group was significantly higher than that in NC group at 1h (p<0.05).Conclusion: (1) Sodium taurocholate retrogressively injected into the pancreatic duct system of Wistar rats caused SAP and most of them had the complication of ALI. BN52021 attenuated SAP and ALI. (2) Pulmonary bronchus epithelial cell in Wistar rats expressed PAF-R. (3) The expression of PAF-R in pulmonary tissues was enhanced in the course of SAP and it indicated that PAF-R was involved in early stage of ALI complicated with SAP. BN52021 had no effect on the expression of PAF-R in pulmonary tissues in the course of SAP and it indicated that BN52021 took its therapeutic effect not by decreasing the expression of PAF-R in pulmonary tissues, but by competitively inhibiting PAF's combination with PAF-R.