Research On Active Components Of Banxiaxiexin Decoction To The Submucosal Healing Mechanism Of Experimental Gastric Ulcer

Objective:In order to study the possible anti-ulcer mechanisms of active components of banxiaxiexin decoction(glycyrrhetinic acid,β-sitosterol,berberine,baicalin and total saponins of panax ginseng)and its orthogonal experimental design compatibility,we compare their difference of efficacy of treating acetic acid induced gastric ulcer and measure the effects of the five active components of banxiaxiexin decoction to the expression of vascular endothelial growth factor (VEGF)and transforming growth factor beta 1(TGFβ₁) of gastric mucosa.Then we select the best active component and the combination of them.Methods:We prepare acetic acid induced gastric ulcer models.Treatment groups must be gavaged by active components of banxiaxiexin decoction and omeprazole after making models.Also we establish normal group,sham-operated control group and model control group.All the rats were sacrificed after half a month.We inspect the ulcer lesion of fresh gastric tissue visually and calculate the ulcer area.At the same time we make the pathological section,normal HE staining and observing the pathological morphologic change.Other fresh gastric tissue should be frozen reserved at -80℃.We adopt the method of RT-PCR detecting the expression level of vascular endothelial growth factor(VEGF) and transforming growth factor beta 1(TGFβ₁).Results:1.Visual inspection:The edge of gastric tissue in rats of model control group are in order.The bottom of gastric tissue is flat and clean.The mucosal plica around uler becomes coarse and stelliform shape;or presents that granulation tissue is outstanding to mucosal surface and not be covered by mucosal epithelium.Gastric mucosa appers impairment,the depth reaching muscularis.There is congestion and edema significantly.Compared to the model control group,the ulcer surfaces in rats of treatment groups are smaller.The edge and the mucosal plica around ulcer are continued.There is congestion and edema of different degree in the mucosal plica around ulcer.Ulcer surfaces in part of rats heal significantly,and are covered by mucosal epithelium.The gastric wall of healed ulcer is thicker than other patrs.2.Pathology:Mucosa covering the ulcerative focus of model control group is little,which is granulation tissue of shallow layer.Most of them apper defect,its depth reaching muscularis. The gap is covered by little generated mucosa,and its gland is arranged in disorder,appering cystic dilatation.There are deep concave ulcer and necrotic thin layer,inflammation exudation layer and scar layer in few of rats.Middle and small arteries in scar layer apper proliferations. Their tube walls are thickening and vascular are stenosis,forming thrombus usually.The vascular structure of submucosal and glands in some of treatment groups are in good condition. The mucosa of ulcer surfaces in most of treatment groups have formed epithelium,lamina propria muscularis and mucosa plica.The depth of mucosa and plica are as same as normal mucosa,though gastric gland are not appering,this tissue covering on ulcer is the healing sign. Mucosa covering on ulcer surface in other treatment groups have formed complete epithelium and lamina propria muscularis.Though the depth of mucosa is a little thiner,the forming morphology of plica is better than model control group significantly.3.Glycyrrhetinic acid,β-sitosterol,berberine and baicalinin in active components of banxiaxiexin decoction all can promote ulcer healing.Compared to the effects of model control group to ulcer area,they have significant differences(P＜0.05).But compared to the therapeutic effects of omeprazole,the differences have no statistical significance(P＞0.05).Glycyrrhetinic acid,β-sitosterol and berberine can increase the expression of VEGFmRNA,and glycyrrhetinic acid can increase the expression of TGF-β₁mRNA,too.But compared to the effects of model control group,they all have no significant differences(P＞0.05).4.The effect to ulcer area of interaction ofβ-sitosterol and berberine in orthogonal experimental design group has statistical significance(P＜0.05).The effect to VEGFmRNA expression of interaction ofβ-sitosterol and total saponins of panax ginseng has statistical significance (P＜0.05).5.The effect to ulcer area,VEGFmRNA and TGF-β₁mRNA expression in interaction of baicalin and total saponins of panax ginseng has statistical significance(P＜0.05).But they can not decrease the ulcer area and increase the expression level of the two positive correlation factor effectively.The combination of them may be inaptitude to clinical treatment of gastric ulcer. Conclusions:1.Visual inspection and pathology show that the healing degree in ulcer surface of treatment groups are better than model control group.The vascular structure of submucosal and glands in of treatment groups are in good condition relatively.2.Glycyrrhetinic acid can decrease the ulcer area,also can increase the expression of VEGFmRNA and TGF-β₁mRNA effectively.Combining the result of pathological section which show that submucous layers are repairing well,so we can conclude that it promotes ulcer healing through increasing the contents of growth factors and the submucosal healing mechanism.3.The combination ofβ-sitosterol and berberine in orthogonal experimental design group can decrease ulcer area effectively.The combination of glycyrrhetinic acid and total saponins of panax ginseng can increase VEGFmRNA expression effectively.We can prove the two combination by further research.4.The combination of baicalin and total saponins of panax ginseng can not decrease the ulcer area and increase the expression level of the two positive correlation factor effectively.The combination of them may be inaptitude to clinical treatment of gastric ulcer.