| BackgroundGastric cancer is one of the common malignant tumors,with an especially higher incidence in East Asia.A large number of epidemiological studies have shown that chronic atrophic gastritis as well as precancerous lesions is correlated with gastric cancer.Therefore,prevention or treatment on atrophic gastritis and precancerous lesions is of great importance for reducing the incidence and mortality of gastric cancer.At present western medicine treatment for chronic atrophic gastritis is mainly symptomatic treatment,while Chinese herbal medicine shows a more remarkable curative effect on atrophic gastritis,which is also a research hotspot currently.As is known to all,inflammation,immune disorders,local hypoxia and angiogenesis all can be the important pathological factors for occurrence of gastric cancer.A number of studies showed that the gastric mucosa of patients with atrophic gastritis may promote the release of various cytokines,thus activating the nuclear factor kappa B(NF-κ B)signals.Therefore,highly active NF-κB signals may play an important role in gastric cancer,which is a tumor-promoting role.In addition,local hypoxia and angiogenesis on gastric mucosa are the most common pathological status of gastric cancer.Lower oxygen/hypoxia is one of the important factors necessary in promoting angiogenesis.Hypoxia inducing factor-1 α(HIF-1 α)and vascular endothelial growth factor(VEGF)are the important biological markers.Research confirms that abnormal activations of NF-κB,HIF-1 α and VEGF are important symbols in occurrence and development of gastric cancer,which are also the potential targets in the treatment of gastric cancer.However,it is rarely reported whether there is abnormal expression of NF-κB,HIF-1 α and VEGF in atrophic gastritis and about the curative effects of traditional Chinese medicine(TCM).Objectives1.To observe the influences of Gastritis I on general behavior of rats with atrophic gastritis;2.To observe the influences of Gastritis I on histopathology of gastric mucosa in rats with atrophic gastritis;3.To observe the influences of Gastritis I on expressions of NF-κBp65 mRNA,NF-κBp65 protein,HIF-1 α and VEGF on gastric mucosa of rats with atrophic gastritis.MethodsRats were randomly divided into blank control group(n = 10),model group(n = 10),vatacoenayme group(n = 13)and gastritis I group(n = 13).Rats of the blank control group was fed regularly,while GPL rat models were established in other groups based on giving MNNG solution and abnormal of starvation and full.The experiment lasted for 18 weeks.The rats began to give gavage from the 9th week.The blank control group and the model group were given distilled water,and the treatment groups were given corresponding drugs for 10 weeks.Gastric mucosal epithelium was taken at the end of the 18th week.Pathological structure of rat gastric mucosa epithelium in each group was observed under optical microscope(hematoxylin eosin staining,HE staining).Fluorescence quantitative reverse transcription PCR(RT-PCR)was used to determine the expression of NF-κ Bp65 mRNA on gastric mucosa epithelium.Immunohistochemistry was used to detect the expression of NF-κBp65,HIF1-αand VEGF.Results1.Rats in the blank group were normal in general,with good mental state,active movement,normal development,burnish fur and normal appetite.Rats in model group were dispirited,whose independent activity was decreased and the development was delayed.Their bodyweight was significantly lower than the rats of blank control group.And their fur was messy and poor in lustrousness.They drank less and had thin sloppy stool or diarrhea.In vatacoenayme group and Gastritis I group,rats showed different degrees of changes in the mentioned performances.2.HE staining showed that no pathological changes were seen in rat gastric mucosa of the blank group.Both glandular structure and cell morphology were normal.Medium to sever atypical hyperplasia can be seen in rat gastric mucosa of model group.Some glandular structure was similar as the adenomatous polyp of the colon.Glandular structure was incomplete.Glandular arrangement was crowded and the boundary was not clear.Atypical cells with different shapes can be seen in glandular lumens.The nuclei of the cells were deep stained and changed into cigar-shape.Pseudostratified change of the nucleus can be seen and the polarity of the nucleus was decreased.For patients with severe lesions,atypical cells were extended to epithelium.Gland lumen showed moderate to severe hyperplasia.Its shape was irregular.There were branches and folding,and polarity of nucleus may often be disappeared.The shape of nucleus was irregular.Thickened cell membranes and prominent nucleoli can be seen while nuclear fission was common.Moderate hyperplasia can be seen in rat gastric mucosal epithelium of vatacoenayme group,which was not obviously compared to the model group.Mild hyperplasia can be seen in rat gastric mucosal epithelium of Gastritis I groups of each dose,which was significantly improved compared with model group.Specifically the glandular structure was mildly changed with a little disorder arrangement and unclear boundary.Lumen cells were less regular in shape.Nucleus was not deeply stained and the size was relatively uniform.Nucleoplasm ratio was imbalance.Polarity of nucleus was weakened,but the nucleus was limited to 1/2 of the base layer.No atypical cells were extended to the surface of epithelium.The nucleus was irregular and nuclear membrane was thickened mildly.Prominent nucleus can be seen while nuclear fission was only seen in the base layer of gastric mucosa epithelium.3.Expressions of NF-κ Bp65 mRNA,NF-κBp65 proteins,HIF-1 α and VEGF in rat gastric mucosa of each group:Expressions of NF-κBp65 mRNA,NF-κBp65 proteins,HIF-1 α and VEGF in rat gastric mucosa of model group were significantly enhanced,which were of statistical significance compared to the blank control group(P<0.05).Compared to model group and vatacoenayme group,expression of NF-KBp65 mRNA on rat gastric mucosa epithelium was significantly decreased in each dose of Gastritis I group and the differences were of statistical significance(P<0.01).Compared to the model group,expression of NF-KBp65 proteins on rat gastric mucosa epithelium was significantly decreased in each dose of Gastritis I group and the differences were of statistical significance(P<0.01).Compared to the vatacoenayme group,expression of NF-KBp65 proteins on rat gastric mucosa epithelium was significantly decreased in high dose of Gastritis I group and the differences were of statistical significance(P<0.05).Compared to the model group,expression of HIF-1 α proteins on rat gastric mucosa epithelium was significantly decreased in high dose Gastritis I group and low dose Gastritis I group and the differences were of statistical significance(P<0.01 or P<0.05).Compared to the model group,expression of VEGF on rat gastric mucosa epithelium was significantly decreased in each dose of Gastritis I group and the differences were of statistical significance(<0.01 or P<0.05).Compared to the low dose of Gastritis I group,expression of VEGF on rat gastric mucosa epithelium was significantly decreased in high dose of Gastritis I group and the differences were of statistical significance(P<0.05).Conclusions1.Gastritis Ⅰ-the compound for tonifying spleen,activating blood circulation and detoxifying not only can effectively improve the symptoms of spleen insufficiency of rats with atrophic gastritis and precancerosis lesions,but also can improve abnormal histopathology status including rat gastric mucosa gland atrophy,intestinal metaplasia and atypical hyperplasia,thus preventing atrophic gastritis and precancerosis lesions from developing invasive gastric cancer.2.The study found that activity of NF-KBp65 was increased in gastric mucosal cells of rats with atrophic gastritis.And HE staining also showed that interstitial hyperemia and edema and lymphocytic infiltration can also be seen in gastric mucosal cells of rats with atrophic gastritis.These suggested that there may be chronic inflammatory change in gastric mucosa of atrophic gastritis rats and may be related to the enhanced activity of NF-KBp65.In addition,gastric mucosal vascular lumen was obviously narrowed under microscopy.There even appeared lumen occlusion or intensive distribution of focal vessels.There was a positive correlation between the severity of structural imbalance of the glands and abnormal degree of blood vessels.These also suggested the correlation between increased HIF-1α and VEGF and pathological changes including new gastric mucosa tube or vascular occlusion or abnormal structure of gastric mucosal epithelial gland.3.Gastritis I may improve the inflammation,local hypoxia and angiogenesis of gastric mucosa of rat with atrophic gastritis by down-regulating the expressions of NF-κB,HIF-1 α and VEGF,and finally improve the abnormal pathological changes of gastric mucosa and achieve the goal of treating atrophic gastritis. |
