The Experimental Studies Of The Effects Of VIP On SAP Gut Barrier Function And Its Possible Mechanism

Objective To explore the effects of VIP on SAP gut barrier function and its mechanism.Methods The models of SAP were induced by retrograde injection of 4% sodium taurocholate into the bili-pancreatic duct. VIP group was made by 5×10-9mol VIP intraperitoneal injection within 5 minutes after SAP model was made. Sham operated (SO) group was made just tipping the pancreas. Fifty four SD rats were randomly divided into the three groups: SAP group,VIP group and SO group. Each group was subdivided into three different time points: 1h,6h,12h respectively and each time point had 6 rats. The VIP in plasma and intestinal homogenate of SO and SAP group were measured by ELISA. The endotoxin in plasma of all groups was also measured. The expression of TNF-αmRNA,IL-6 mRNA,IL-10mRNA in intestinal mucosa were measured by RT-PCR , and TLR4 expression was also measured by RT-PCR and immunohistochemistry. Meanwhile intestinal samples were harvested for pathological and electroscopic examination.Results (1) Compared with SO group, the VIP in plasma and intestinal homogenate of SAP group were obviously decreased at 1h after intervention, and then gradually increased to surpass the level of SO group at 12h(p<0.05).(2) The endotoxin of SAP group was continually increased compared with SO group, but in VIP group the endotoxin was decreased compared with the same time point of SAP group, especially at 6h after intervention(p<0.01). There is no statistical difference between other time points. (3)The expressions of TNF-αmRNA,IL-6 mRNA,IL-10mRNA and TLR4 were also increased in SAP group, with obvious pathological and electroscopic injuries in the intestine. In the VIP group, the expression of TNF-αmRNA,IL-6mRNA and TLR4 was suppressed while IL-10mRNA was increased. The intestinal pathological and electroscopic injuries were also markedly alleviated, especially at 6h after intervention(p<0.05).Conclusions (1) The VIP in plasma and intestinal homogenate of SAP were gradually increased after temporal decreasing which was possibly demonstrated as compensatory response and it maybe play a great role in alleviating the SAP pathogenesis. (2) VIP can efficiently protect SAP gut barrier function by down-regulating TLR4 expression and inhibiting the excessive inflammatory reaction.