| Objective:To evaluate the clinical effect of Shidan granules on precancerous lesion of gastric Cancer(PLGC)patients before and after self-effect comparison.A rat PLGC model was established to observe the effect of Shidan granules on pathological of gastric mucosa,the position and degree of positive expression of NF-? B p65,and the changes of NF-? B p65 and IKK? protein content in tissues,so as to explore the possible mechanism of Shidan granules on PLGC.Methods:Into the group of 30 PLGC patients based on clinical diagnosis and inclusion criteria were treated by Shidan granules.After six months,the symptom scores and endoscopic features before and after treatment were compared.70 Wistar male rats as the experimental rats that were randomly divided into normal group(n=10),model group(n=60).The model rats are established by 150ug/mL MNNG,0.03%ranitidine pelletized and 0.1%ammonia feed for 28 weeks.After the model was established succesfully,10 rats in the normal group continued to feed on the standard diet till the end of the experiment.The remaining rats of the model group were randomly divided into 5 groups:model group(0.9%Nacl),western medicine group(0.3g/kg/d Vitacoenzyme Tablets)and Shidan granules low dose(14.04g/kg/d),middle dose(28.08g/kg/d),and high dose(56.16g/kg/d).Except for the normal group of normal feeding,the rest rats are gavaged for next 12 weeks,then all rats are killed,and gastric tissue samples were collected.Observation of pathological morphology of gastric mucosa by H&E Staining.Immunohistochemistry was used to determine the expression level of NF-?B p65 and the degree of expression.The expressions of NF-?B p65 and IKK? protein were detected by western blotting.Results:The clinical observation results showed that(1)30 PLGC patients were treated with Shidan Granules for 6 months.The results showed that:a total efficiency of 73.3%.(2)The clinical symptoms of the patients after treatment were significantly improved(P<0.01),and the total effective rate was 93.3%.(3)Gastroscope pathology:Shidan Granules had significant improvement in gastric mucosal atrophy and intestinal metaplasia(P<0.01);There is a certain improvement in the intraepithelial neoplasia.The results of the experimental study showed that:(1)General condition of rats:The rats in the blank group had good conditions,normal food intake,and stable weight gain.Rats in the model group were sparsely populated with poor activity,decreased weight and slow weight growth and even lost weight.With drug intervention,the general state of the rats was better than before.(2)Pathological observation of rat gastric mucosa:The pathological histology changes:normal gastric mucosa structure level complete set,closely packed glands and rules;In the model group,the mucous layer was obviously thinned,the number of the inherent glands was reduced,and even with intraepithelial neoplasia;Shidan granules group and western medicine group had intact gastric mucosa structure,moderate thickness,regular arrangement of glands,atrophy,intestinal metaplasia,no dysplasia.(3)Expression of NF-?B p65:The mean optic density(MOD)of NF-?B p65 positive cells in the model group is higher than normal group(P<0.01).In contrast,the NF-?B p65-positive cells in the Shidan granule group and the western medicine group were mainly expressed in the cytoplasm and the MOD was decreased(P<0.01).The MOD of the positive cells in the low,middle,and high dose groups of Shidan granules was sequentially decreased,the MOD of low-dose group was slightly higher than the western medicine group(P<0.01);the middle-dose group had no significant difference with the western medicine group(P>0.05);(4)the expressions of p65 and IKK? protein:compared with the blank group,the expressions level of p65 and IKK? in the model group were significantly increased(P<0.01),while there was no significant difference in the level of p65 protein between Shidan granules high-dose group(P>0.05).Compared with the model group,the expressions of p65 and IKK? in Shidan granule group and western medicine group decreased significantly(P<0.01);The protein levels of p65 and IKK? in low,medium,and high dose of Shidan granules decrease in turn,and with a statistically significant difference between the three groups(P<0.01).The protein expressions of p65,IKK? in western medicine group and Shidan middle dose group water had no significant difference(P>0.05).Conclusion:(1)The clinical observation shows that Shidan granules can effectively improve the clinical symptoms of patients with PLGC,significantly improve gastric mucosal atrophy and intestinal metaplasia,and the reversal of intraepithelial neoplasia is not yet clear,pending further study;(2)Shidan Granules significantly improved the pathological of gastric mucosa in PLGC rats.There were dose-effect differences between different dose groups of Shidan Granules.Increased drug concentration,better efficacy.(3)The mechanism of Shidan Granule in the treatment of PLGC may be through inhibition of IKK expression,to reduce the abnormal activation of NF-?B,blocking the nuclear transcription pathway. |
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