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The Study On The Clinical Distribution Of Non-steroidal Anti-inflammatory Drug-related S Gastric Mucosal In Jury And Its Correlation With Microrna Expression

Posted on:2018-04-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y S HongFull Text:PDF
GTID:1314330512499644Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Background and Purpose:Non-steroidal anti-inflammatory drug-related gastritis(NSAIDs related gastritis),refers to taking non-steroidal anti-inflammatory drugs after gastric mucosal injury,from mild erosion to peptic ulcer and other pathological changes,severe cases may occur gastrointestinal Bleeding and other acute and critical.Non-steroidal anti-inflammatory drugs with fever,anti-inflammatory,analgesic,inhibition of immune and other effects,are widely used in various types of rheumatic immune diseases and various types of cold fever patients,aspirin clinical use is very extensive,as the first line of coronary heart disease Medication,although the selective non-steroidal anti-inflammatory drugs,but its extensive use of the digestive tract side effects has been the concern of clinicians.As the modern eating habits and lifestyle changes,the incidence of cardiovascular and cerebrovascular disease increased year by year,while rheumatic immune diseases,metabolic diseases(especially gouty arthritis)incidence is increasing year by year,and was younger Trend,due to the lack of national drug regulatory system,civic health awareness is generally weak,leading to non-steroidal anti-inflammatory drug clinical abuse,peptic ulcer bleeding high clinical symptoms.There are popular surveys show that the elderly because of their physical dysfunction,cardiovascular and cerebrovascular disease multiple,long-term use of aspirin,gastric mucosal protection decreased,taking non-steroidal anti-inflammatory drugs complicated by gastrointestinal ulcer bleeding significantly increased the risk of clinical treatment Large,the mortality rate is higher than the common ulcer bleeding.A large number of clinical and basic studies have shown that Helicobacter pylori(HP)infection and ulcer is closely related to the occurrence of gastric cancer can also be a contributing factor,HP infection is non-steroidal anti-inflammatory drug-related stomach problems occur important factors,the latest A prospective study of HP infection with non-steroidal anti-inflammatory drugs related to the stomach of the relevant research,HP infection with non-steroidal anti-inflammatory drugs used to lead to the incidence of stomach disease,therefore,for HP with NSAID Early prevention and intervention of related diseases is extremely important.In recent years,MicroRNA related research more and more attention,a large number of studies have shown that,MicroRNA involved in the cell's physiological changes,and gastric mucosal injury are closely related.The high expression of microRNA-21(miR-21)was associated with nuclear factor transport factor(NF-KB),and it was found in the tutor group that non-steroidal anti-inflammatory drugs could inhibit prostaglandin E and activate NF-?B pathway,NF-?B pathway activation can lead to IIL-6,IL-8,TNF-? and other inflammatory factors released in large numbers,leading to acute inflammation of the gastric mucosa,the existing related research,MicroRNA-21 as an upstream pathway,The expression of miR-21 is closely related to the expression of NF-?B protein and may be related to the expression of mucin in gastric mucosa.The mucin is closely related to Helicobacter pylori infection.Therefore,this study suggests that miR-21 may Non-steroidal anti-inflammatory drug-related gastropathy.In this study,the relationship between miR-21 expression and Helicobacter pylori infection was also discussed.At the same time,the gastric mucosa and miR-21 expression.Non-steroidal anti-inflammatory drug-related stomach disease belongs to the category of "epigastric pain" in Chinese medicine.Epigastric pain in the disease under the xiphoid,epigastric Department,the disease in the stomach,stomach for the cavity of the organs,to pass for the use of its main gas reduction,stomach and spleen phase,the spleen for the day after tomorrow This is the main Shengqing,spleen or stomach down,mediation in the gas machine,gas machine is smooth and healthy,if the gas lift and loss,poor air,poor pain;Blood of the source of blood,spleen and stomach weak,blood and raw health,Qi deficiency,not Rong is pain;Qi deficiency to promote blood line,Qi blood stop,stomach stasis,not through the pain.Non-steroidal anti-inflammatory drug-related gastrointestinal disease in the spleen and stomach,the pathogenesis of folder is true,the cause of mostly fruiting body deficiency,combined with exorcism invasion,external virtual,so the treatment on the basis of tonic,Supplemented by exorcising pain.In this study,under the guidance of the theory of TCM syndrome differentiation and treatment,the TCM syndromes of nonsteroidal anti-inflammatory drug-related gastropathy were taken as the starting point to explore the distribution pattern of TCM syndromes,and the syndromes were combined with western medicine basic experimental study.To investigate the relationship between the expression of miR-21 and the possible existence of TCM syndromes in non-steroidal anti-inflammatory drug-related gastric mucosa.To this end,the purpose of this study is:(1)Through the study of the symptoms of non-steroidal anti-inflammatory drug-related gastric disease and the characteristics of tongue and tongue,the distribution of TCM syndromes was discussed.(2)To investigate the infection of Helicobacter pylori in non-steroidal anti-inflammatory drug-related stomach patients in this study.(3)To investigate the histopathological changes of gastric mucosa and the distribution of diseased parts of non-steroidal anti-inflammatory drug-related gastropathy in this study.(4)To investigate the relationship between the expression of miR-21 and the incidence of non-steroidal anti-inflammatory drug-related gastric disease in gastric mucosa of this study.(5)To explore the correlation between Helicobacter pylori infection and miR-21 expression and mucin secretion in this study.(6)To investigate the expression of miR-21 and the distribution of TCM syndromes in gastric mucosa of non-steroidal anti-inflammatory drug-related gastric disease in this study.(7)To investigate the relationship between the expression of miR-21 and the expression of NF-?B P65 in non-steroidal anti-inflammatory drug-related gastric disease in this study.(8)To explore the correlation between TCM syndromes and NF-?B P65 protein expression in non-steroidal anti-inflammatory drug-related gastric disease in this study,(9)To investigate the expression of inflammatory cytokines and mucin in non-steroidal anti-inflammatory drug-related gastric diseases;(10)To investigate the relationship between the expression of MiR-21,NF-?B and cell inflammatory factors and mucin in non-steroidal anti-inflammatory drug-related stomach.Research methods:(1)Subjects:From 2016 to 2017,the patients with rheumatology,cardiovascular and spleen-stomach "epigastric pain" of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine were included in the study according to the inclusion criteria and exclusion criteria.;(2)All eligible "epigastric pain" patients were at the First Affiliated Hospital of Guangzhou LUniversity of Traditional Chinese Medicine endoscopy endoscopy,and take biopsy,gastric mucosal specimens,while excluding atrophic gastritis,early cancer and other lesions;(3)All eligible patients underwent 13 carbon breath test or 14 carbon breath test to determine HP infection;(4)All eligible patients under the guidance of the doctor in the sub-high or above,take the form of a double control,through the four Chinese medicine syndrome differentiation,to identify non-steroidal anti-inflammatory drug-related patients with TCM syndromes;(5)The relative expression of miR-21 in gastric mucosal samples was detected by qRT-PCR(real-time quantitative PCR)(6)The relative expression of mucin in gastric mucosa was detected by flow cytometry.The expression of NF-?B in gastric mucosa was detected by Western Blot.(7)The levels of IL-6,IL-8 and TNF-? in gastric mucosa were detected by enzyme-linked immunosorbent assay(ELISA)(8)The correlation between TCM syndromes and miR-21 expression was analyzed by statistical method.(9)The correlation between TCM syndromes and NF-?B expression was analyzed by statistical method.(10)Statistical analysis of the correlation between miR-21 and NF-?B in Helicobacter pylori infection;(11)The correlation between the expression of miR-21 and the expression of NF-?B was analyzed statistically.(12)on the expression of miR-21 and the expression of IL-6,IL-8 and TNF-?were analyzed statistically.Research result:(1)non-steroidal anti-inflammatory drug-related gastrointestinal endoscopic often showed gastric mucosal congestion and edema,Such as local or large area erosion,or submucosal bleeding,or local scattered ulcer changes in the pathology and more performance for acute inflammation or erosion changes,accompanied by neutrophils and other inflammatory cell infiltration.The ratio of single to gastric antrum was 58.93%;the ratio of single gastric body(including gastric angle)was 1.79%;the ratio of single to gastric fundus was 21.43%;the whole stomach(gastric antrum,stomach angle,stomach Body,stomach)ratio of 17.86%.According to the degree of mucosal injury classification,chronic gastritis with erosion changes accounted for 58.93%;erosive = hemorrhagic changes in the proportion of 39.29%;ulcerative changes in the proportion of 1.79%.(2)non-steroidal anti-inflammatory drug-related stomach patients with tongue distribution characteristics:pale tongue,thin whiteThe proportion of 38.36%;tongue red moss yellow tired of the proportion of 17.85%;tongue with or without teeth covered with greasy moss greasy accounted for 25%;tongue red moss or crack moss accounted for 7.14%Dark brown(or side with ecchymosis)accounted for 5.36%.The distribution of pulse is as follows:the proportion of pulse thin or fine is 33.93%;the proportion of slippery or chord is 17.85%;the proportion of pulse string is 5.36%;the proportion of pulse delay is 25.00%Accounting for the proportion of 7.14%;TCM syndromes distribution characteristics:the proportion of spleen and stomach qi 33.93%;liver and stomach does not account for the proportion of 5.36%;the proportion of blood stasis 10.76%;spleen and stomach accounted for 17.85%The proportion of loss of 7.14%;spleen and stomach Deficiency accounted for 25.00%.(3)Helicobacter pylori infection in nonsteroidal anti-inflammatory drug-related stomach patients:positive(+ or++)accounted for 87.5%of the patients;negative(-)patients accounted for 12.5%of all patients.Different types of non-steroidal anti-inflammatory drug-related stomach disease with HP infection:spleen and stomach qi deficiency patients infected with HP was 89.47%;liver and stomach disability test HP infection rate was 66.67%;blood stasis infection HP The positive rate was 83.33%;the positive rate of HP infection was 90%;the positive rate of HP infection was 50%;the positive rate of HP infection was 78.57%in patients with spleen deficiency syndrome.(4)The expression of miR-21 in gastric mucosa of patients with non-steroidal anti-inflammatory drug-related stomach disease was 43.50 ± 10.02,The relative expression of miR-21 in the gastric mucosa of the blank control group was 17.83 ± 1.99,which was statistically significant(P = 0.000<0.05),indicating that the expression of gastric mucosa was higher in nonsteroidal anti-inflammatory drug-related gastric patients The relative expression of miR-21 in gastric mucosal tissue of H.pylori infection was 34.90 ± 7.05;the relative amount of miR-21 expression in gastric mucosa of patients with Helicobacter pylori positive was 49.90 ± 6.26;normal blank The relative expression of miR-21 in the gastric mucosa of the control group was 18.28 ±2.33.The relative expression of miR-21 in the HP negative/positive group was statistically different from that of the normal blank control group(P<0.05).(-)vs(+)= 0.675;PC = 0.000).The results showed that the non-steroidal antiinflammatory drug-related gastropathy had higher expression of miR-21 in gastric mucosal tissues with or without Helicobacter pylori infection.(5)The relative expression of miR-21 in gastric mucosa of patients with spleen and stomach deficiency was 48.39 ± 8.36.The relative expression of miR-21 in gastric mucosa was 45.14 ± 12.31;The relative expression of miR-21 in gastric mucosal tissue was significantly higher than that in control group(P<0.05).The relative expression of miR-21 in gastric mucosa was 33.19 ±10.67.Compared with the spleen-stomach qi deficiency group,spleen-stomach damp-heat group and other syndromes group,it can be seen that the relative expression of miR-21 in spleen-stomach dampness group and spleen-stomach group was higher than that in other syndromes group The relative expression of miR-21 in gastric mucosal lesion was not significantly different between spleen and stomach qi deficiency group and spleen-stomach damp-heat group.(6)The expression of NF-?B in gastric mucosa was 0.63 ± 0.15 in non-steroidal anti-inflammatory drug-related gastric disease.The expression of NF-?B in gastric mucosa was 0.22 ± 0.08 in normal blank control group,Statistically significant,suggesting that non-steroidal anti-inflammatory drug-related gastric disease in patients with gastric mucosal NF-KB expression.The relative expression of NF-?B p65 in gastric mucosal lesion was 0.70 ± 0.92 in H.pylori,and the expression level of NF-?B p65 in gastric mucosal lesion was 0.57 ± 0.21 The expression of NF-?B p65 in gastric mucosa of normal control group was 0.24 ± 0.09.The expression of NF-?B p65 in gastric mucosa of non-steroidal anti-inflammatory drug-related gastric lesions was significantly higher than that in blank control group(P(-)vs(+)=0.298).There was no significant difference in the expression of NF-?B p65 in the gastric mucosa of HP(-)and HP(+)0.000)(7)The relative expression of NF-?B p65 in gastric mucosa of patients with spleen-stomach deficiency syndrome was 0.65 ± 0.13.The relative expression of NF-?B p65 in gastric mucosa was 0.70 ± 0.11,The expression of NF-?B p65 in the gastric mucosa was significantly higher than that in the control group(P<0.05).The expression of NF-?B p65 in the gastric mucosa was significantly higher than that in the control group KB p65 was 0.46 ± 0.19.Compared with the spleen-stomach deficiency group and the spleen-stomach damp-heat group and other syndromes group,it was found that the relative expression of NF-?B p65 in spleen-stomach damp-heat group and spleen-stomach qi deficiency group was higher than that in other patients There was no significant difference between the two groups(P>0.05).There was no significant difference in the expression of NF-?B p65 between the spleen and stomach qi deficiency group and the spleen-stomach damp-heat group.(8)non-steroidal anti-inflammatory drug-related gastric disease in patients with gastric mucosal inflammation factor IL-8 tableAnd the level of IL-8 in the gastric mucosa of the normal control group was 2.11 ± 1.36,the difference was statistically significant.The non-steroidal anti-inflammatory drug-related gastropathy patients had an inflammatory factor IL-6 expression level was 17.94 ± 9.74,the expression level of inflammatory cytokine IL-6 in gastric mucosa of normal control group was 5.23± 1.48,the difference was statistically significant;non-steroidal anti-inflammatory drug-related gastric disease in patients with gastric mucosal tissue The expression of TNF-? in the gastric mucosa of the normal control group was 1.15 ± 1.79,the difference was statistically significant.The results showed that the expression of TNF-? was significantly higher than that of the control group(P<0.05)The expression of IL-8,IL-6 and TNF-?in the gastric mucosa of patients with gastropathy was increased,which indicated that the gastric mucosa of non-steroidal anti-inflammatory drug-related gastric disease had obvious inflammatory response The(9)In this study,the correlation coefficient was compared with the original data,The correlation between the relative expression of miR-21 and the relative expression of NF-?B protein in gastric mucosa was expressed by the correlation coefficient,and the correlation coefficient r was used to express the correlation coefficient r The value range is limited to-1 and +1,the correlation coefficient r closer to 0 that deviate from the correlation and the correlation is smaller,the correlation coefficient r closer to +1 that the greater the positive correlation,the opposite correlation coefficient r closer to-1 The greater the negative correlation.The results showed that there was a positive correlation between the expression of MiR-21 and the expression of NF-?B in the gastric mucosa of patients with non-steroidal anti-inflammatory drug-related gastric disease.The correlation coefficient r was +0.91 and P-0.02.Ana lysis conclusion:(1)non-steroidal anti-inflammatory drug-related gastrointestinal endoscopy often manifested as gastric mucosal congestion and edema,plaque-like changes,or local or large area erosion,or submucosal bleeding,or local scattered multiple ulcers change,pathology Manifested as acute inflammation or erosion changes,accompanied by neutrophils and other inflammatory cell infiltration,the lesion site to the common gastric antrum,also see the whole stomach lesions,lesions to erosion-based,"whole stomach or antral mucosal erosion Gastritis".(2)In this study,non-steroidal anti-inflammatory drug-related stomach patients with tongue to "pale tongue thin white" and "red tongue yellow greasy moss" mainly pulse "pulse thin" and "pulse string slippery "he main,combined with the characteristics of the symptoms and tongue pulse analysis,we can see non-steroidal anti-inflammatory drug-related stomach disease syndromes to the actual situation both to" spleen and stomach "and" spleen and stomach qi deficiency ";(3)In this study,the infection rate of Helicobacter pylori in nonsteroidal anti-inflammatory drug-related gastric disease was,suggesting that Helicobacter pylori infection was associated with the incidence of non-steroidal anti-inflammatory drug-related gastropathy;(4)In this study,miR-21 was highly expressed in non-steroidal anti-inflammatory drug-related gastric disease,indicating that miR-21 expression was associated with the incidence of non-steroidal anti-inflammatory drug-related gastropathy;(5)In this study,the infection of HP in patients with nonsteroidal anti-inflammatory drug-related gastropathy was not significantly correlated with miR-21,suggesting that Helicobacter pylori infection did not affect the expression of miR-21 The occurrence of steroidal anti-inflammatory drug-related gastropathy;(6)In this study,the expression of miR-21 in gastric mucosa was higher than that in other syndromes,and the expression of "spleen-stomach damp-heat syndrome" and "spleen-stomach qi deficiency syndrome" in non-steroidal anti-inflammatory drug-related gastropathy There was no significant difference between the two syndromes,indicating that spleen deficiency and dampness may lead to the up-regulation of miR-21 expression in diseased tissue,leading to the progression of non-steroidal anti-inflammatory drug-related gastropathy.(7)In this study,NF-?B P65 protein was significantly higher in non-steroidal anti-inflammatory drug-related gastric lesions and had a positive correlation with miR-21 expression,suggesting that miR-21 expression up-regulated NF-?B pathway,while promoting the development of non-steroidal anti-inflammatory drug-related gastric inflammation;(8)The expression of NF-?B P65 protein in the two types of non-steroidal anti-inflammatory drug-related stomach disease,spleen-stomach damp-heat syndrome and spleen-stomach qi deficiency syndrome was higher than that of other syndromes,Leading to high expression of NF-?B P65 protein in the tissue,increased release of inflammatory cytokines,leading to the occurrence of non-steroidal anti-inflammatory drug-related inflammation of the stomach.In summary,the distribution of non-steroidal anti-inflammatory drug-related stomach syndromes was mainly composed of spleen-stomach qi deficiency and spleen-stomach dampness,and both of these syndromes showed high expression of miR-21 and NF-?B P65 protein,The expression of miR-21 and NF-?B P65 protein was significantly correlated with the expression of NF-?B P65 protein,and the expression of miR-21 pathway may play an important role in the expression of NF-?B P65 protein,-?B pathway,resulting in IL-8,IL-6 and TNF-? and other large increase in the release of cytokines,tissue inflammation changes,leading to non-steroidal anti-inflammatory drug-related stomach disease occurrence and development.
Keywords/Search Tags:Non-steroid-associated gastropathy, micRNA expression pathway, TCM syndromes distribution, pathogenesis
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