| Research background:Gastric Ulcer (GU) is a common clinical acute and chronic digestive diseases,it refers to the festering and fragmentary damage on the surface of gastric mucosa,which was caused by the desquamation of the local tissue. With the in-depth study of etiology and pathogenesis of gastric ulcer,and the the rapid development and wide application of effective drugs for the treatment of gastric ulcer, the incidence of gastric ulcer show a gradual downward trend, the incidence of serious complications also decreased. However, easy recurrent of gastric ulcer is still a clinical problem to be solved. If the prevention and treatment was not properly,it may cause serious complications such as bleeding, pyloric obstruction, etc. How to improve the quality of ulcer healing and reduce the recurrence, become the research focus of the majority of clinicians.The pathogenesis of gastric ulcer is very complex, Gastric ulcer belongs to the category of "stomach ache","acid reflux","noisy" in Traditional Chinese Medicine (TCM). It was regarded by the TCM that a lot of factors such as exterior pathogenic factor attacking stomach, uncontrolled eating and drinking,bad mood, hypofunction of the spleen and stomach and so on,these factors may cause the dysfunction of spleen and stomach and impaired digestive function,If this situation continues,the function of the spleen and stomach may tangled, circulation of qi and blood may disorders, impassable channels and collaterals of stomach may cause the stomach ache.It was regarded by the modern medicine that gastric ulcer is caused by a lack of equilibrium between the gastric aggressive factors and the mucosal defensive factors.when the aggressive factor enhanced and (or) the mucosa defense function abated,this balance will be breaked,and gastric ulcer will happen.Traditional Chinese Medicine for the treatment of peptic ulcer has the advantage of less side effect and low recrudescent rate,etc.High attention has been paid to this field.Oxygen free radical (OFR) is a kind of oxygen containing group with high chemical reaction activity which produced by the oxygen insufficient to accept electron when reduction,it’s the internal oxygen’s incomplete metabolite and one of the most important gastric ulcer attack factors.In gastrointestinal tract, the content of xanthine dehydrogenase is more than any other tissue,it’s easy to produce superoxide free radical by xanthine-xanthine oxidase system,phagocyte respiratory burst, aldehyde oxidase or other pathway,so some people compare the gastrointestinal tract as a ticking time-bomb of producing oxygen free radicals. Superoxide dismutase (SOD) is the scavengerenzyme of superoxide anion, Its function is catalyze the disproportionated reaction of oxygen free radical,transform the superoxide anion radical as hydrogen peroxide and oxygen,eliminates the function of superoxide anion radical,reduce the damage of excessive superoxide anion to the human body,reduce the affect of radical to unsaturated fatty acid,reduce the production of lipid peroxides,play the protective function to the body. Oxygen free radical act on lipid form the lipid peroxide,maleic dialdehyde (MDA) is the product of lipid peroxide decomposed.As the sign of oxidation,the content change of MDA can reflect the extent of tissue injury by free radicals indirectly.We can find out the metabolism of the internal oxygen free radicals indirectly by detecting the vitality of SOD and the content of MDA in the blood serum.Weiweifang(WWF) is professor Liu Xiaowei’s empirical prescription,It has been proved that WWF has a good antiulcer effect in clinic.In this experiment,we detected gastric mucosa, ulcer size and gastric ulcer circa histopathologic slide to find out WWF’s Therapeutical effect.The vitality of SOD and the content of MDA in the blood serum were detected.The purport is to find out the correlate treatment mechanism of WWF. We hope that we can support experiment evidences for WWF’s clinical apply and exploitation.Experimental methods:1、Fifty-six male Wistar rats of SPF level and at the weight of200-250g are divided into7groups according to a completely random method. Those are normal group, model group, self-healing group, ranitidine group,WWF group with high, medium and low dose.In each group, there are8rats. Models were prepared according to the classic glacial acetic acid method, and transformed. The diet of rats is not restricted for3days,and then begin to surgery.the rats must fast diet more than24hours before operated on but with mormal drinking.Inject intraperitoneally10%of chloral hydrate to anaesthetize rats, prepare for abdominal skin and fix the rat on the anatomy board,then disinfect with alcohol of75%and iodine tincture of2%and pave surgical gauze.Cut one2.0cm-2.5cm longitudinal incision since xiphoid along ventral,remove the stomach from the enterocoelia gently and expose it,and paste acetic acid-soaked filter in diameter of5mm in the tunica serosa gastria for30seconds twice and absorb the residual glacial acetic acid with dry cotton balls,wash the stomach softly with cotton swab moistened with saline water,then put the stomach back to the enterocoelia. suture the wound layer by layer, disinfect the wound with iodine tincture of2%again, the surgery finished.2、The normal group eating and drinking freely, execute and take samples after15days; The rest groups will be operated after daptive feeding for3days except the normal group,the model group execute and take samples on the fourth day after being operated; begin to perfuse stomach on the fourth day after being operated for7days;self-healing group eating and drinking freely after being operated, execute and take samples after7days with Each treatment group.Observe the healing processes of gastric ulcer with eyes,observe gastric ulcer histopathologic slide with optical microscope,and measure the area of ulcer, detect the vitality of SOD and the content of MDA in the blood serum. 3、The experimental results are expressed by mean±standard deviation(x±s). SPSS13.0software was applied into One-way ANOVA for mean comparison based on multiple samples.Take Levene homogeneity test for variance first,when the variance was homogeneous, Least-significant difference was applied for test, when the variance was not homogeneous,take welch test to adjust,use Dunnett’s T3test.The value of P<0.05would mean significant difference.Major findings:1、Gross observations of gastric mucosaGastric mucosa of the normal group rats were pink,integrity and smooth, without congestion, edema,ulcer,hyperplasia of scar tissue or other abnormal changes. Gastric mucosa of model group rats were congested and dropsical,stomach of most rats were stick to hepar or other tissue nearby,ulcer can be find on the gastric mucosal,the center of the ulcer was coverd by purulent secretion of yellow or white colors. Gastric mucosa of self-healing group rats were congested and dropsical,stomach of some rats were stick to hepar or other tissue nearby,hard to separate,the healing of the ulcer is not so good,dark red hyperplasia of scar tissue can be seen.The serosal surface of the ranitidine group rats have some adhesion,the surface of mucosal is rough and erosion point can be seen around the adhesion.In groups of WWF with high and low dose rats’ gastric mucosa were little congestive beside the molding area,irregular ulcer and hyperplasia of scar tissue can be seen on the gastric mucosal.The ulcer of WWF medium dose group rats were healing well,it’s hard to find the ulcer on the surface of gastric mucosal or only localized hyperplasia of scar tissue can be find.2、Observation with optical microscopeGastric mucosa of normal group rats were smooth,with gland in order. Inflammatory cells could not be observed. Gastric mucosa of model group rats were not intact,and the gland was disorganized,large amount of inflammatory cells infiltrated the submucosa and serosa,capillary vessel under ulcers were blocked and bleeding.In self-healing group,muscular mucosal were even defected and regenerative glandular cells arranged disorderly,there were inflammatory cells infiltration, granulation tissue were disordered.In ranitidine group,the coloboma were smaller and new epithelial cells and glandular cells arranged irregularly on the surface,submucosa was infiltrated with inflammatory cells,irregular new granulation tissue can be seen in muscular layer. In groups of WWF with high and low dose, defects of the gastric mucosawere smaller,the density of glandular cells were asymmetrical,with little inflammatory cells infiltration,there were no significant pathological changes in submucosal blood vessels. In groups of WWF with middle dose,mucous membrane was almost integral and fewer inflammatory cells infiltration in submucosa,the granulation tissue was in order.3、Comparison of ulcer areaComparing with model group,the ulcer area of ranitidine group,WWF high,middle and low dose groups was obviously reduced (P<0.01);Comparing with self-healing group,the ulcer area of ranitidine group,WWF high,middle and low dose groups was obviously reduced (P<0.01);The difference was statistically between ulcer area of WWF with middle dose group and ranitidine group(P<0.05).4、Comparison of the vitality of SODThe SOD vitality of model group rats was obviously less than normal group rats(P<0.05);Comparing with model group rats,the SOD vitality of WWF middle dose group rats increased significantly(P<0.05); Comparing with self-healing group, the SOD vitality of WWF middle dose group rats increased significantly(P<0.05).5、Comparison of the content of MDAComparing with model group rats, the MDA content of WWF high,middle and low dose group rats was significantly decreased(P<0.01); the MDA content of self-healing group was obviously lower than model group rats(P<0.05); Comparing with self-healing group, the MDA content of WWF middle dose group rats was significantly decreased (P<0.05); Comparing with ranitidine group, the MDA content of WWF high and middle dose group rats was significantly decreased (P<0.01).Conclusion:1、Establish a stable experimental animal models is basis to ensure scientific accuracy and reliability.This research use acetic acid induced gastric ulcer models to study, gastric mucosa was eroded by acetic acid directly,blood circulation was affect, local tissue became necrosis and dropped out, result to ulcer formation.This modeling method with high success ratio is simple and easy to copy,the ulcer witch need long time to recover is deep and large,and similar to human’s chronic gastric ulcer,it’s useful to observe the effect of therapy,this method is a standard and common modeling method.2、Gross observations of gastric mucosa and measurement of the ulcer area remind us that the best form of ulcer is model group rats,the mode achievement ratio is reach100%,the healing of all the treatment group rats is better than self-healing group rats,the cure effect of WWF middle dose group is the best of all groups,the ulcer area was significantly reduced.3、Observation of the gastric ulcer histopathologic slide with optical microscope remind us that gastric mucosal tissue structure change of model group rats is most obvious,the mucosal defect is serious, the healing of all the treatment group rats is fine,especially the WWF middle dose group rats, the healing of self-healing group rats is not so good.4、Comparison of the SOD vitality and the MDA content suggests that in the process of ulcer formation, the SOD vitality of rats decreased and the MDA content increased,after treated by middle dose of WWF, the SOD vitality increased and the MDA content decreased.It suggests that middle dose of WWF can increase the SOD vitality and decrease the MDA content, get rid of the internal oxygen free radical, promote the healing of ulcer.In conclusion, this experiment copy the model of experimental rats with gastric ulcer successfully,by observing the gastric mucosal,observing of the gastric ulcer histopathologic slide with optical microscope, measuring the ulcer area,detecting the vitality of SOD and the content of MDA in the blood serum,we found that WWF has a good therapeutic effect on experimental gastric ulcer in rats,we suppose that WWF may have the effect of getting rid of the internal oxygen free radical, increasing the SOD vitality and decreasing the MDA content.But the therapeutic effect not show a quantity-efficiency relation,the effect of middle dose is the best. |
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