The Study On Effects And Mechanisms Of WTL On Anti-stomach Ulcer

The patient of gastric ulcer often show the typical ache of midsection with the periodic, other symptoms include distension and fullness,eructation,regurgitation,nausca and vomiting. The familiar complications are bleeding,perforation and pyloric obsrictio etc..Peptic ulcer in Traditional Chinese Medicine mostly belongs to the category of"weiwan tong"(stomachache),"outu"(vomiting). Peptic ulcer can be divided into the type of Qi-stagnation,Heat-stagnation,Blood stasis,Yin-insufficiency,Insufficiency-cold,Replenshing Qi to inrigorate the spleen and Regulating Qi to Dispel stasis is the basic method to cure this disease, according to cause of disease of different and respectively over-emphasize is Cleaning away pathogetic heat of the stomach,Nourishing the stomach-Yin,Warming the middle energicer to Dispel cold.Fiborscope examination is a main diagnostic method. Although there are various treatments that have a lot of irregularity .According to the drugs safety principle, the first chooser is still oral administration pharmaceutical. The purpose of this experiment is that investigate the anti-ulcer effects and the possible mechanism of Wetailing capsule.Objective: To study the effects and mechanisms on the Weitailing Capsule of the rats in experiment on anti- stomach ulcer .Methods:Experiment1:The effect of Weitailing Capsule to the constrainted- stressing ulcer in rats .Fifty rats(25 females and 25 males)with a weight range of 190-250 gwere used for the experimentation.The rats were fed with standard laboratory chow and water before experiment .Rats were divided into 5 equal groups(n=10)and housed in cages . Groups 1 as control group and groups 2 as model group were administered with 10ml·kg-1distilled water,group 3, groups 4, groups 5 were administrated with differents dose 1000mg/10ml/kg, 500mg/10ml/kg, 250mg/10ml/kg Weitailing, ALL of drugs were administered by gavage at the same volume (10ml·kg-1/d). Administrating 7 days consecutively, and no supply but water 24 hours to every rats after administration in the sixth day.After the last administration 2 hours, to lightly anesthetize the rats by diethyl ether ,and then to tie the rats'limbs to the iron net.Let the rats'head down vertically 16 hours,and then to put them to death by decapitation. After ligate the cardia of stomach and the pylorus,take the whole stomach out from the abdominal cavity, and then inject 10ml 0.9%saline sodium into the stomach.Then soaking the stomach into the Formalin (1%) to fix 5 minutes, and then cut the stomach along the curvatura gastrica major.To unfold the curvatura gastrica major on the glass plate after using water to wash it. At last , to caculate the level of the ulcer and assay the contents of MDA,NO,GSH and the activity of SOD in the rat's serum and gastric mucosa.Experiment 2:The effect of Weitailing Capsule to ligated-pylorus gastric ulcer in ratsTaking 80 rats with a range of (190-250g) were used for the experimentation.The rats were fed with standard laboratory chow and water before experiment . Rats were divided into 8 equal groups(n=10)and housed in cages . Administrating the capsule to the rats with a dosage from the table2 during 7 days,two times every day and 20ml·kg-1/d.But administrate thesame volume of distilled water to the control group and the model group.After sixth day administration,then no supply but water to the rats during 24 hours.Then anesthetize the rats by diethyl ether and ligate the pylorus of stomach . No any supply to the rats water after the ligating .Put the rats to death by decapitation and ligate the cardia of stomach after 18 hours, Then take out the stomach and collect the gastric fluid,record the capacity of the gastric fluid and measured the total gastric acid,free acid and the activity of pepsinum.At last , scissoring the stomach along the greater curvature of stomach.Wash it and then unfold it on the glass plate to caculate the level of the ulcer.Experiment 3:The therapeutical effect of Weitailing Capsule to acetic acid- gastric ulcer in ratsTaking 100 rats to sterilize ,operate and Lightly pull the stomach out the outide of abdomen after anesthetize the rats by diethyl ether under no supply but water for 48 hours,then inject 0.05ml acetic acid(10%) to the depth of tunica subserosa gastria 0.4～0.5mm between the body of stomach and pyloric antrum and inject 0.05ml physiologic saline to the control group.Then return the stomach to the abdominal cavity of the rats and sew up the abdominal.The next day,divide the rats into 5 equal groups and lavage the capsule to the rats with the dosage from the table2,two times every day, 10ml·kg-1 per time(lavage the control group and the model group the same volume of distilled water).Continue administration during 14 days. Before 2 hours administrating , we put the rats to death by decapitation. Then ligated the cardia of stomach and the pylorus,took the stomach out and soaked it into the Formalin (1%) for 10 minutes. After that, we cut the stomach along the greater curvature of stomach and evert it to eliminate thecontents.Using tubule to wash away the food residue,and then observe the extent of ulceration in the corresponding sites of membrana mucosa injected Acetic acid solution,caculat the ulcer index(the mean of the longest and the shortest diameter of ulcer).At last ,taking the others rats to ligate the cardia of stomach and the pylorus.then take the stomach out and soak it into the Formalin (1%) to fix,paraffin imbedding,HE dyeing,observe by the light microscope and measured.Experiment 4:The effect of Weitailing Capsule to inducible-gastric ulcerin rats .Taking 50 rats ,at the same level randomly divide into 5 groups and lavage with the dosage from the table 3,two times a day and 10ml·kg-1 per time(lavage the same volume of distilled water to the control group and the model group. Continue administration 7 days . After the administration in the fifth day,there is no supply but water during 48 hours.then taking the idomethine dissolve to 5 %NaHCO3 and diluting to suspl (2mg·1ml-1)by distilled water.Inject the prepared suspl to the rats from subcutaneouly of the back at the dosage of 20 mg/kg.After 6 hours, put the rats to death by break off the rats'ceruical uertebra.To open the abdomen cavity to ligate the cardia of stomach and the pylorus,and then take the stomach out and inject 10ml formalin(1%) to it.After that ,soak the stomach into formalin(1%) 5 for 10 minutes to fix it .Then cut the stomach along the greater curvature of stomach and clean it by water,observe and note the information of the damage of gastric mucous membrane.Using the sum of the ulcer in lengh millimeter as the ulcer index to statistical treatment,and then caculating the percentage of the inhibition of ulcer to evaluate the drug action.RESULT:Experiment 1:To stress ulcer,the ulcer index of the medication administration groups is obviously lower than the model group,the contents of GSH,NO are show significantly in the medication administration group and increased the activity of SOD additionally the weitailing capsule was found to prevent the rise in MDA level .Experiment 2:To ligated-pylorus gastric ulcer, the ulcer index of the medication administration groups is also obviously lower than the model group and the percentage of the inhibition of ulcer is 56.3%,25.0% and 20.8% respectively.It illustrates that Weitailing Capsule have the obvious inhibitory action to ligated-pylorus gastric ulcer, as well as the action to the total gastric acid,free acid and the Peptic activity of stomach.It can decrease the effect of attacked factors to gastric wall,but has n't any effection to the volume of gastric fluid.Experiment 3:The Weitailing Capsule can inhibit the development of the acetic acid- gastric ulcer and promote the progress of concrescent.The mean of the longest and the shortest diameter of the ulcer of the high dose group and the middle dose group is obviously less than the model group.According to the results of the observation of the shape ofulcer rats and quantitation ,the model group rats'gastric mucous membrane defects more serious,the lamina muscularis mucosae at some extent of crack,the bottom of ulcer becomes more thicker and the regeneration of the epithelium mucosae of ulcer is not obvious, itindicates that the duplicate of the gastric ulce model is successful .The groups of high dose,middle dose and low dose can ease the defect of gastric mucous membrane,the width of the crack of lamina muscularis mucosae and the thickness of the bottom of ulcer,it also can make the epithelium mucosae around the ulcer regenerate and be filled with granulation tissue. The pathological changes shows that the Weitailing Capsule can significant inhibit the acetic acid- gastric ulcer , especial the high dose group has the best effect .Experiment 4:To inducible ulcer ,the gastric ulcer index of high dose groups and middle dose groups is obviously lower than the model groups,the percentage of inhibition of ulcer is 65.2% and 42.8% respectively .It illustrates that the Weitailing Capsule has the conspicuous inhibitory action to induced gastric ulcer.Results:Weitailing(250mg-1000mg/kg)could decrease Ulcer index and the level of NO,GSH and the activity of SOD obviously increased in serum and gastric mucosa as compared with the model group and have obvious relation in dose-dependent mannes. By oral administration of Wtl(250mg-1000mg/kg) time after time , Wtl could apparently enhance section magnitude of free mucus and gastric wall mucus in rats` stomaches. the gastic acid and the active of pepsin, were both inhibited. We can see it from the compare of morphological observation of the rat's pathological tissue whose model of gastic ulcer were acetic acid-induced with the results of mensurable measure that gastic mucosa layer was ruptured in different degree ,the thickness of ulcer bottom were increased ,theepithelium of gastric mucosa around the ulcer regeneration was't obvious.Conclusions: Weitailing could obviously inhibited the formation of the gastric ulcer induced by stress.It is suggested that antiulcer mechanism of Wtl may relate to increasing the level of NO and GSH and inhibiting the production of free radicals,Weitailing also obviously increased structure maturity and the fuction of mucous glucoprotein on gastric wall, accelerated the healing of rat`s ulcer. Imcomplete of gastric mucosa layer,the breath of rupture muscle mucosa layer ,the thickness of the bottom of ulcer were lightened in various degree by the high dose ,middle and low of the capsule of Weitaling compound ;and at the same time ,the epithelium of mucosa around the ulcer regeneration,area of ulcer was filled by granulation tissue.The path-changing indicated that the capsule of Weitaling compound ameliorate the grastic ulcer acetic aiced-induced in rats especial the high dose.