Therapeutical Effect Of Weiweifang (WWF) On Acetic Acid-inducted Gastric Ulcer And The Dependablity Study Of Plasma Neurotensin(NT) In Rats

Background:Peptic ulcer(PU) disease is one large kind of digestive system diseases, which spreads cosmopolitism. It has been estimated that 5%～10% people have suffered this disease in their lives. The pathogenesy is complicit. It has been summarized that the balance is destroyed between aggression factor of gastric mucosa intestinal mucosa and mucosa self defend- reparative factor. PU has the characteristics of long course of disease, ease palindromia and some severe complication.Gastric acid inhibition and gastric mucosa protectant are two main methods of clinical therapeutics. At present, histamine-2-receptor antagonists and proton pump antagonists which widely use in clinic make GU accrete rate predominance raise. However, the problem of cost, side-effect, drug resistance, patient dependence makes the GU palindromia high. Therefore, GU therapeutics is still a urge and important task. Recently, the exploitation of GU drug turns to naturally occurring drugs.Weiweifang(WWF) is Liu Xiaowei professor's empirical formula. It has been proved that it has a good effect to GU in clinic. Qijifang(QJF) is one part of WWF .The experiment which bases the Traditional Chinese Medicine(TCM) theory and clinical effect adopts acetic acid—inducted gastric ulcer mode. We detected gastric mucosa, ulcer size and gastric ulcer circa histopathologic slide to find out WWF's Therapeutical effect. The gastric fluid pH, serum gastrin(Gas) and plasma neurotensin(NT) concentration had been detected. The purport is to find out the correlate treatment mechanism of WWF. NT which has hol-modulation function is the enter-point in our experiment. We hope that we can support experiment evidences for WWF's clinical apply and exploitation.Methods:1. Acetic Acid-Induced Gastric ulcerThe experiments were performed according to the method described by Takagi et al., with some modifications. Eight groups of male Wistar rats that had fasted for 24 h were used in this experiment. Under anesthesia, a laparotomy was performed on all animals through a midline epigastric incision. After exposing the stomach, filter pape in 5 mm area with 100% acetic acid solution was contacted with the subserosal layer in the glandular part of the anterior wall. The abdomen was then closed and all animals were fed normally.2. Rats subgroup and relative indicatrix detectionSeventy two male SPF Wistar rats were randomly divided into nine groups of 8 each, respectively marked with normal group, model group, autotherapy group, Ranitidine group, WWF groups and QJF groups. Normal group is untreated and freely drink and eat. Model group is inducted gastric ulcer by acetic acid and freely drink and eat. When acetic acid—inducted gastric ulcer in rats of autotherapy group, Ranitidine group, WWF groups and QJF groups , the groups which drink and eat freely are respectively treated with nothing, but Ranitidine, three different doses of WWF (low ,medium , high ) and two different doses of QJF (medium , high )7 days. Except model group in the forth days, other groups are killed in the eleventh day. Afer they are killed, We detected the gastric fluid pH, gastric mucosa, ulcer size, gastric ulcer circa histopathologic slide, serum gastric acid secretion(Gas) and plasma NT concentration.Stastical analysis:The data result of study is analysis with SPSS11.5 statistics software. The data is expressed with (x|-)±S. One-Way-ANOVA is used to multiple comparisons. Comparison in gastric ulcer area, when the test of Homogeneity of vriances is not existent we use Welch test and that the group's disparation is existent, we use Dunnett's T3 test. Comparison in gastric fluid pH in rats, when the test of Homogeneity of vriances and the group's disparation is existent, we use LSD test. Comparison in serum Gas in rats, the test of Homogeneity of vriances is existent but the group's disparation is not existent, so we do nothing. Comparison in plasma NT concentration in rats, when the test of Homogeneity of vriances is not existent we use Welch test and that the group's disparation is existent, we use Dunnett's T3 test.Results:1. Gastric mucosa detected with eyes , for no equipmentThe ulcer of WWF medium dose group (WWFMG) is almost healing, neogenesis tissue has nothing different with normal tissue. There are only light aphthae and little inflammatory exudate seen.2. comparision in drug groups and autotherapy group in gastric ulcer area in ratsThe test of Homogeneity of vriances is not existent. It is used Welch test and that the group's disparation is existent, we use Dunnett's T3 test. Drug groups includes Ranitidine group, Weiweifang low dose group (WWFLG),WWFMG, Weiweifang high dose group(WWFHG), Qijifang medium group (QJFMG), Qijifang high group (QJFHG) have discrepancy significantly compared with autotherapy group (P=0.005, P=0.028,P=0.001,P=0.007, P=0.001, P=0.001) .WWFMG has discrepancy significantly compared with Ranitidine group (P=0.013) . WWFMG, QJFMG, QJFHG have discrepancy significantly compared with WWFHG (P=0.006, P=0.043, P=0.036) .The effective of WWF is not rely quantity in gastric ulcer area.3. To detect gastric ulcer circa histopathologic slide in light microscope.WWFMG's mucosa is almost integrity. Only a few of ulcer which is small in area reach the juncture of endepidermis and gastric area glandularis. The recovery of cellula epithelialis and glandular organ are fine, glandular organ Cellular proliferation is nice, include quantity , space, alignment. There are a few of inflammatory cell infiltration in mucosa underlayer. Microcirculation has not significant patho-change. Muscular layer turn to slide. Granulation tissue grow in regularity. A few of serosa membrane are abruptly.4. Comparison in gastric fluid pH in rats.When the test of Homogeneity of variances and the group's disparation are existent, we use LSD test. Model group, QJFMG,QJFHG have discrepancy significantly compared with normal group (P=0.006, P=0.000, P=0.034) . WWFMG has not discrepancy significantly compared with normal group (P=0.746) .All the groups can divide in three levers of pH. Normal group, Ranitidine group and WWF groups are in the low lever, autotherapy group is in the middle lever. Model group and QJF groups are in the high lever.5. Comparison in serum Gas in ratsThe test of the Homogeneity of vriances is existent but the group's disparation is not existent, so we do nothing.6. Comparison in plasma NT concentration in ratsThe test of the Homogeneity of vriances is not existent. We use Welch test and that the group's disparation is existent, we use Dunnett's T3 test. Model group, Ranitidine group, WWFLG, QJFMG and QJFHG have discrepancy significantly compared with autotherapy group (P=0.021, P=0.020, P=0.032, P=0.016) . Autotherapy group and WWFHG have discrepancy significantly compared with model group (P=0.021, P=0.003) . All groups have not discrepancy significantly compared with normal group. WWFMG is close to normal group (P=1) .All the groups can divide in three levers of NT. Model group, Ranitidine group, WWFLG and QJF groups are in the low lever. Normal group and WWFMG are in the middle lever. Autotherapy group and WWFHG are in the high lever. The effective of WWF has the tendency to rely quantity in plasma NT concentration in rats (r=1, P= 0.002) .Conclusion:1. The mode achievement ratio is reach 100% in gastric ulcer area in rats. Autotherapy group has bad effect. All the drug groups have more or less therapeutical effect. WWFMG has the best effect.2. Because of compatibility and dose, WWF groups and QJF groups have complicate dose-effect relationship. It manifests that compatibility and dose of Tradition Chinese drags in same specification are important to therapeutical effect.3. WWFMG has the best therapeutical effect by detecting the gastric mucosa with eyes, for nothing equipment.4. WWFMG has the best therapeutical effect by detecting gastric ulcer circa histopathologic slide in light microscope. It has good effect in microcirculation, anti-inflammatory and cell regeneration.5. In plasma NT concentration, model group is lower than normal group. It manifests that the synthesis and release of NT is in lower lever in elcosis.6. Model group is higher in gastric fluid pH than normal group. It manifests that acetic Acid-Induced Gastric ulcer is a stress for rats. For self-protect, rats irritably remove the equilibrium mechanism to counteract Acetic Acid. It may be the reason why the model group is in higher lever in gastric fluid pH. 7.The effective of WWF has the tendency to rely quantity in plasma NT concentration in rats (r=1, P=0.002) , but not in serum Gas . It manifests that NT can effect the gastric mucosa during the treatment period, but not through Gas derectly. It may be through growth hormone release inhibiting hormone (GIH) .8. QJF groups have discrepancy significantly compared with WWF groups in gastric fluid pH. It proves that solitude use with notoginseng and bletillae rhizome can elevate pH to inhibit the gastric acid secretion. When QJFMG and WWFLG are in the same lever, but lower than normal lever in plasma NT concentration, QJFMG have better effect through the higher pH.9. WWFMG is close to normal group in gastric fluid pH, serum Gas and plasma NT concentration. From the evidence of gastric ulcer circa histopathologic slide, WWFMG has the best effect in recovering damaged gastric mucosa, Partial mechanism is that plasma NT may be playing a hol-regulation role by anti-inflammatory, microcirculation improvement and cell regeneration.10. WWFMG is close to normal group in plasma NT concentration(P=l). It has been supposed that plasma NT which exist leak point close to normal concentration play an important role for gastric mucosa. Plasma NT in this concentration can regulate the body as to normal.In above, it has been find out that WWFMG has the best effect by detecting gastric mucosa, ulcer size, gastric ulcer circa histopathologic slide. Partial mechanism is that plasma NT may be playing a hol-regulation role by adjusting pH to normal lever and by anti-inflammatory, microcirculation improvement and cell regeneration.