Clinical Observation Of Huazhuo Jiedu Huoxue Decoction In The Treatment Of Chronic Atrophic Gastritis And Experimental Study On NF-κB Signaling Pathway

Part One:Professor Liu Qiquan’s Academic Thoughts on Treating Chronic Atrophic Gastritis by Treating Chronic Atrophic GastritisObjective:Based on the theory of"Huazhuo jiedu huoxue",this paper discusses the academic thoughts of the Professor Liu Qiquan on the treatment of chronic atrophic gastritis（CAG）.Methods:Through the analysis of the"Zhuodu Xueyu"syndrome of Huazhuo Jiedu huoxue Recipe,Professor Liu Qiquan’s thoughts on the etiology and pathogenesis of CAG,the treatment methods and the rules of clinical medication were summarized.Results:Professor Liu Qiquan believed that the etiology and pathogenesis of CAG were:turbid toxin content is the mechanism of onset;weakness of the spleen and stomach is the basis of the onset;stagnation of qi and blood stasis is the tendency of chronic illness.Treatment should start with the methods of dispelling dampness,invigorating the spleen and stomach,dispelling blood stasis,and detoxifying heat.At the same time,the treatment of CAG can be achieved through micro dialectics and concurrent syndromes.Summary:Professor Liu Qiquan deeply cultivates the classics and is good at summarizing.He believes that the formation and progress of CAG are closely related to both"turbid toxin"and"blood stasis".The method of removing turbidity,detoxification and promoting blood circulation is used in the clinical treatment,which has significant curative effect and good results..The tutor’s academic thoughts on the treatment of CAG from the theory of"removing turbidity,detoxification and promoting blood circulation"enriched its treatment methods and provided theoretical basis for follow-up clinical research and animal experiments.Part Two:Clinical Study on Treatment of Chronic Atrophic Gastritis with Huazhuo Jiedu Huoxue DecoctionObjective:To evaluate the clinical efficacy of Huazhuo Jiedu Huoxue Decoction（HZF）on patients with turbid toxin and blood stasis CAG and its effect on pepsinogen,aiming to verify the effectiveness and safety of Huazhuo Jiedu Huoxue Decoction in the treatment of CAG.The possible mechanism of action will be discussed preliminarily.Methods:Sixty-six patients with CAG turbidity and blood stasis syndrome who met the diagnostic criteria were enrolled and randomly divided into treatment group（HZF group）33 cases and control group（Morodan group）33 cases according to the order of treatment.The medication treatment course was 24 weeks,and the changes of pathological tissue scores,primary and secondary symptom scores,symptom curative effect scores,serum pepsinogen changes,and adverse reactions were recorded in detail before and after treatment.Results:After drug intervention,the gastric mucosal pathology scores of the two groups were improved,among which the HZF group was better than the Morodan group（P<0.05）;the symptom scores of the HZF group were significantly lower than those before treatment,and it alleviated stomach pain,fullness,and fullness.The belching is better than the Morodan group（P<0.05）,and it is better than the Morodan group in improving secondary symptoms such as noisy heartburn,dry mouth,bitter mouth,nausea and vomiting,and anorexia（P<0.05）;after treatment,the total symptoms of two groups were lower than before treatment,among which the HZF group was lower than that of the Morodan group（P<0.05）;in terms of the efficacy of TCM syndromes,the total effective rate of the HZF group was 93.75%,which was higher than 77.42%of the Morodan group（P<0.05）.In terms of gastroscopic efficacy,the total effective rate of the HZF group was 87.50%,which was higher than 74.19%of the Morodan group（P<0.05）;in terms of pathological efficacy,the total effective rate of the HZF group was 81.25%,which was higher than the 64.52%of the Morodan group（P<0.05）.After treatment,the PGⅠand PGR values of the HZF groups significantly higher than before treatment（P<0.05）.The PGⅠand PGR values of the HZF group after treatment were significantly higher than those of the Morodan group（P<0.05）,and the PGⅡvalues of the two groups after treatment has no significant change（P<0.05）.During the treatment of the two groups of patients,there were no adverse reactions,no abnormality was indicated in various indicators,and the drugs were safe and reliable.Summary:Huazhuo Jieduhuoxue Decoction has definite curative effect in the treatment of turbid toxin and blood stasis CAG.It has obvious advantages in improving the pathological conditions of the gastric mucosa and the symptoms of patients with major and minor symptoms,and is safe.The application of this formula broadens the research and differentiation of thoughts and provides basis for clinical application and research of Chinese medicine.Huazhuo Jieduhuoxue Recipe can significantly increase the levels of PGⅠand PGR,indicating that the patient’s pepsinogen level is related to the occurrence and development of CAG.Its mechanism of action may be related to the effect of HZF on gastric mucosal cell proliferation and gastric mucosal repair by regulating the level of pepsinogen and gastric acid secretion.Part Three:Study of Huazhuo Jiedu Huoxue Recipe on NF-κB Signal Pathway in CAG RatsObjective:To observe the effect of Huazhuo Jieduhuoxue Fang（HZF）on rats with chronic atrophic gastritis（CAG）,and to explore its mechanism of preventing and treating CAG.Methods:Methods:60 SD healthy male rats were induced by MNNG combined modeling method to induce CAG model.After successful modeling,they were randomly divided into blank group,model group,HZF high(29.40g·kg^-1),medium(14.70 g·kg^-1)Low(7.35 g·kg^-1)dose group and Morodan group(0.05 g·kg^-1),blank group and model group were given the same amount of normal saline,once a day,continuous intervention for 12 weeks.After the administration,HE staining was used to observe the pathological changes of the rat gastric mucosa,the contents of interleukin-1β（IL-1β）,interleukin-6（IL-6）and tumor necrosis factor-α（TNF-α）in serum of rats were detected by enzyme-linked immunosorbent assay（Elisa）.Western blotting（Westernblot）,real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）and immunohistochemical（IHC）were used to detect m RNA and protein expression of NF-κB signaling pathway in each group.Result:Compared with the blank group,the model rats were slow to respond,clustered and curled up,hair was dim and shedding,appetite was reduced,lethargy or even irritable,loose stools and sticky stools;compared with the model group,Huazhuojieduhuoxue Fang and Morodan rats are sensitive,lively and active,with bright white hair,normal appetite,good mental state,and granular stools,which can significantly improve the general conditions of the rats;most of the gastric mucosal glands in the model group are atrophied,the number is reduced,and the mucosal layer Thinning,with inflammatory cell infiltration,intestinal metaplasia,goblet cells,dysplasia of individual glands,and lymphoid follicle formation;HZF high-dose group has moderate gastric mucosa thickness,regular gland arrangement,and inflammatory cell infiltration Less;compared with the blank group,the serum levels of IL-1β,IL-6,and TNF-αin the model group increased to varying degrees,and the levels of NF-κB（p65）,COX-2,Cyclin E,and IKK in the gastric tissue of rats m RNA and protein expression levels increased to varying degrees（P<0.05）;compared with the model group of rats,the serum levels of IL-1β,IL-6,and TNF-αin each group were decreased to varying degrees（P<0.05）,the m RNA and protein expression of NF-κB（p65）,COX-2,Cyclin E,and IKK-αin gastric tissues all decreased to varying degrees,especially in the high-dose group of Huazhuo Jieduhuoxue Decoction and The rodan group decreased significantly（P<0.05）..Summary:Huazhuo Jiedu Huoxue Recipe can down-regulate the NF-κB signaling pathway,reduce the release of inflammatory factors and reduce their protein expression,thereby blocking the activation and conduction of inflammatory cells;and it can regulate the abnormal activation of downstream target genes of NF-κB signaling pathway,and then inhibit its downstream gene mutation,so as to achieve the purpose of prevention and treatment of CAG.Conclusion:1.It is concluded that Professor Liu Qiquan believes that the occurrence and development of CAG is closely related to"turbid toxin and blood stasis".The prescription and use of medicine shows that turbidity and blood stasis is the key to pathogenesis,and"clearing heat and detoxification,promoting qi and blood"throughout the treatment.The empirical formula of removing turbidity,detoxification and activating blood can be used in the treatment of CAG by kneading dampness,invigorating the spleen and stomach,removing blood stasis and evil,and antipyretic toxin.It can eliminate the pathogenesis and restore the function of the stomach and intestines to achieve the treatment purpose of shrinking and reversing the process of cancer.2.Clinical observations show that HZF can improve the histopathological state of the gastric mucosa,improve gastric mucosal atrophy and intestinal metaplasia in a certain extent,and it has a significant effect in relieving the clinical symptoms of patients and has good safety.HZF can significantly increase the levels of PGⅠand PGR,which may be achieved by regulating the level of pepsinogen,affecting the proliferation of gastric mucosal cells,gastric mucosal repair and gastric acid secretion.3.In terms of animal experimental research,experiments were carried out from rat serum inflammatory factors and NF-κB signaling pathway related indicators to study the mechanism of Huazhuo Jieduhuoxue Fang’s prevention and treatment of CAG.The HZF high-dose group has a significant effect,which may be related to its ability to regulate serum inflammatory factors and reduce the expression of NF-κB signaling pathway related indicators m RNA and protein.By inhibiting the expression of inflammatory factors and related proteins,cell activation and conduction are blocked,thereby to achieve the purpose of preventing and controlling CAG.