Synergetic Effect of Yihuo Qingyi Decoction (益活凊胰汤) and Recombinant Staphylokinase in Treatment of Severe Acute Pancreatitis of Rats

Objective: To investigate the effect of recombinant staphylokinase (r-Sak) and the Chinese medicine Yihuo Qingyi Decoction (益活凊胰汤 Herbal decoction for severe acute pancreatitis) in the treatment of the severe acute pancreatitis (SAP) in rats, and to observe the synergistic effect of the two. Methods: One hundred and sixty-two adult male SD rats with the body mass of 250–280 g were randomly divided into the following 5 groups: sham operation group (n=18), control group (n=36), Yihuo Qingyi Decoction treatment group (n=36), r-Sak treatment group (n=36), and Yihuo Qingyi Decoction plus r-Sak treatment group (n=36). The SAP ratmodel was prepared by retrograde injection of 5% sodium taurocholate into the cholangiopancreatic duct. Two days before modeling, Yihuo Qingyi Decoction was intragastrically administrated, and r-Sak was intraperitoneally injected. The survival rate within 18 h after modeling was determined. The pancreatic blood flow, the weight of ascites, and the serum amylase and lipase were investigated at 6 h, 12 h, and 18kh after modeling, and the pancreatic tissue was examined under light microscopy to see its pathological change. Results: The 18 h survival count of group A,B,C,D and E rats was 9,2,6,7 and 8 respectively. After r-Sak and Yihuo Qingyi Decoction intervention, the serum amylase and lipase and the weight of ascites were significantly decreased, especially in group E.18 h after modeling, the level of the serum amylase and lipase and the weight of ascites in group E was 1 100±118 U·L-1,1 000±150 U·L-1 and 13.40±1.80 g respectively, obviously lower than that of group B (P<0.05).After SAP was induced, the pancreatic blood flow showed a tendency to decrease, but the decrease extent in the treatment groups was smaller than that in the control group.18h after modeling, the pancreatic blood flow in group B and group E was 30.16±8.96 mL·100 g-1·min-1,and 129.10±42.58 mL·100 g-1·min-1 respectively, there was significant difference (P<0.05). The pathological change of the pancreatic tissue was alleviated in the treatment groups. Conclusion: Both r-Sak and Yihuo Qingyi Decoction play a beneficial role in the treatment of rat SAP and there is a synergistic effect between the two.

Pharmacokinetics of Native r-SAK in Rabbit's Femoral Artery Thrombosis Model

Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.