OBJECTIVETo investigate the therapeutic effect of Qingyi Decoction (QYD) and tetrandrine (Tet), used singly or combind, in treating miniature pigs with severe acute pancreatitis (SAP) and its mechanism.

METHODSThirty-two Guizhou miniature pigs were made into SAP model by pancreatic duct retrograde injection of 5% sodium taurocholate. They were randomly divided into 4 groups: the control group, the QYD group, the Tet group and the combined treated group. The serum amylase activity and interleukin-1 and 6 (IL-1, IL-6) contents in serum from vena cava and portal vein were tested by biochemistry and radioimmunoassay (RIA). Serum emodin and plasma Tet levels were measured by high performance liquid chromatography (HPLC) 24, 48 and 72 hrs after treatment. And the pathological changes of pancreas, lung and liver were observed under microscope.

RESULTSThe mortality of SAP pigs was reduced significantly and the inflammatory injury of the organs was ameliorated obviously in all treated groups, and the increased amylase activity and IL-1, IL-6 levels was attenuated. The therapeutic effect was much more obvious, and the plasma Tet level at different time points were much higher in the combined treated group than those in the other two groups treated by single drug (P < 0.01).

CONCLUSIONBoth QYD and Tet could treat effectively SAP through multiple pathways, combination of them reveals an elevation of serum drug concentration and shows a synergistic effect.

Alkaloids ; blood ; pharmacokinetics ; therapeutic use ; Animals ; Benzylisoquinolines ; blood ; pharmacokinetics ; therapeutic use ; Drug Synergism ; Drugs, Chinese Herbal ; pharmacokinetics ; therapeutic use ; Emodin ; blood ; Female ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Male ; Pancreatitis, Acute Necrotizing ; blood ; drug therapy ; Phytotherapy ; Random Allocation ; Swine, Miniature

OBJECTIVETo observe the effects and mechanism of Qingyi II Granules (QYG) on the bacterial translocation in rats with acute necrotizing pancreatitis (ANP).

METHODSEighteen Sprague-Dawley rats were randomized equally into 3 groups, the sham-operated group (A), the ANP model group (B) and the treated group (C). Rats in Group B and C were established into ANP model by retrograde injection of 30 g/L sodium taurocholate into pancreatobiliary duct. QYG was administered, beginning from 1 h after modeling, for three times (every 6 h) per day via intragastric infusion to Group C in dose of 10 mL/kg (250 g/L), while to the other two groups, equal volume of saline was infused instead. All animals were sacrificed 24 h after modeling. The contents in mesenteric lymph nodes and distant sites (liver, spleen, pancreas) were taken for bacterial culture and strain identification, the expression of high mobility group box 1 (Hmgb1) mRNA in ileal tissue was assayed by real-time PCR; the levels of nitric oxide (NO) and endothelin-1 (ET-1) were determined by ELISA; the wet/ dry ratio of ileum was measured; and the pathologic features of pancreas and ileum were examined respectively.

RESULTSIn Group B, evident pathological injury in pancreas and ileum was shown, expression of Hmgb1 mRNA up-regulated, levels of NO and ET-1 in ileum tissues increased to 1.67 +/- 0.21 micromol/L and 102.18 +/- 9.19 ng/L respectively, and the bacterial counts in the mesenteric lymph nodes and distant sites increased significantly. Compared with Group B, the level of NO and ET-1 reduced to 1.39 +/- 0.23 micromol/L and 83.15 +/- 5.39 ng/L, respectively in Group C, with all the above-mentioned abnormal changes alleviated significantly.

CONCLUSIONLevels of Hmgb1, NO and ET-1 might play important roles in the ANP model rats with intestinal bacterial translocation. QYG shows effects on preventing the intestinal bacterial translocation by way of down-regulate the Hmgb1 mRNA expression, lowering the concentration of NO and ET, and ameliorating the injury of pancreatic and ileum tissues.

Animals ; Bacterial Translocation ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Endothelin-1 ; analysis ; HMGB1 Protein ; metabolism ; Intestinal Mucosa ; microbiology ; Intestines ; microbiology ; Nitric Oxide ; analysis ; Pancreatitis, Acute Necrotizing ; drug therapy ; microbiology ; Phytotherapy ; Rats ; Rats, Sprague-Dawley