Model Development Of Syndromes Suitable For Tiaoweichengqi And Xiaochengqi Decoctions Using Lab Rabbits

The objectives of this study were to(a) develop animal models that could be adequately used to show the syndromes suitable for Tiaoweichengqi Decoction(SSTD) and Xiaochengqi Decoction(SSXD),which are the "Excess-Syndrome of yangming disease" as described in the traditional Chinese medical literature;(b) establish applicable methodology for the model-building using lab rabbits;(c) define objective criteria for the syndrome observation;and(d) discuss the possible mechanism and meaning of the drug's medicinal effects.The study was carried out with 105 lab rabbits by equally and randomly dividing the animals into 7 groups.The groups included Control(1),Pathological Model of SSTD(2A), Model-Treating of SSTD(2B),Model-Proving of SSTD(2C),Pathological Model of SSXD (3A),Model-Treating of SSXD(3B),and Model-Proving of SSXD(3C).Normal feed was given to the rabbits in the Control group.Feed containing varying amounts of bismuth subcarbonate were given to the Model groups for 2 days,no water for 24 hours on the second day,then intravenously injected E.coli endotoxin.An hour before and 2 hours after the endotoxin injection,physiological saline was given orally to Groups 2A and 3A.For Group 2B and 3B,Tiaoweichengqi Decoction(TD) and Xiaochengqi Decoction(XD),respectively, were given orally.In the 2C and 3C groups,TD or XD was given when the bismuth subcarbonate containing diet and the endotoxin were administered.During the experiment,a rabbit's spirit,breath,ear blood vessel,body temperature and abdominal circumference were observed or measured regularly.Blood samples were collected for testing from the rabbits 6 hours after endotoxin injection.At the end,air was injected into the vein to kill the animals. Pathological changes in lung,liver,intestines and kidney were examined under microscope.The results indicated that no changes incurred to the animals in the Control group. There was a rise in body temperature among the rabbits in Group 2A and 3A,with those in 2A the most significant.The abdominal circumference of the animals in Group 2A and 3A significantly enlarged,with those in 3A the greatest increase.There were significant differences(P＜0.01 or P＜0.05) on all indices between the Control and Model groups.The WBC counts and the contents of NO,MDA and MMS in 2A and 3A animals increased in various degrees,whereas the SOD decreased.The K and Na contents decreased in varying amounts in the Model groups.The viscosities of the whole blood and plasma increased while erythrocyte deformation index decreased in the Model groups.In Group 2A and 3A,t-PA content decreased,as PAI-1,TXB₂ and TM contents increased.Comparing Group 2A and 3A to the other groups,there existed significant differences(p＜0.05 or p＜0.01).Certain indices showed significant differences(p＜0.05 or p＜0.01) and others no difference in Model-Treating groups and Model-Proving groups as compared to the Control.Pathological observations during the experiment included(a) most of the animals in Group 2A and 3A had bleeding spots in the lungs;(b) large bowels were distended with gas;and,(c) there was no apparent change in other viscera.Microscopic observations were:(a) local lung consolidation seen in Group 2A,and to a lesser degree in Group 3A animals;(b) congestion and leukocytes infiltration existed in lung tissue with pulmonary septal thickened;(c) varying degrees of congestion and leukocytes infiltration found in the intestinal mucosa;(d) some leukocytes infiltration observed in the liver but no changes in the kidney;(e) either slight or no changes found in the rabbits in the Model-Treating or Model-Proving groups.It was concluded that the multifactor intervention approach with varying dosages of bismuth subcarbonate,water deprivation and endotoxin injection could create the major symptoms,physiological signs and pathological changes in lab rabbits strikingly close to what described by the TCM theories.Thus,this method of developing models seemed appropriate for the purpose.In addition,TD and XD showed to be effective in lowering body temperature, reducing abdominal circumference,and alleviating disease symptoms and abnormal physiological signs on the infected rabbits.They could also improve various testing indices and pathological changes.These,again,correspond well with the TCM theories.Thus,the reliability of the model-developing method was proven.