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The Relationship Between TLR2,TLR4 Expression On Peripheral Blood Mononuclear Cells And Small Intestinal Bacterial Overgrowth In Patients With HBV Related Hepatocellular Carcinoma

Posted on:2019-02-25Degree:MasterType:Thesis
Country:ChinaCandidate:D X ZhouFull Text:PDF
GTID:2334330545989586Subject:Internal medicine
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BackgroundHepatocellular carcinoma(HCC)is one of the common and deadly clinical disea se,which seriously threatens people's health.Epidemiological investigation identified that almost 90 percent of HCC were HBV infection.It has been reported that bac terial translocation,small intestinal bacterial overgrowth and a high level of plasmat ic endotoxin is a common finding in the chronic liver disease.Toll-like receptor(TL Rs)was regarded as a pattern recognition receptor and plays an important role in t he host immunity against microbe infection.Increasing evidence suggest that the de velopment of HCC is closely associated with the persistence of chronic inflammatio n,in which TLRs mediate the immune and inflammatory reaction may play a cruci al role in this process,however the exact machanism is still unclear.ObjectiveTo investigate the expression of TLR2 and TLR4 on peripheral blood mononuc lear cells(PBMCs)in HBV related hepatocellular carcinoma and the relationship wi th SIBO.MethodsBetween August 2015 and August 2017,46 cases of patients with HBV relate d hepatocellular carcinoma,35 cases of chronic hepatitis B(CHB)and 16 cases of healthy people were observed in our department.Flow cytometry analysis was used to detect the expression of CD14~+monocyte surface TLR2/TLR4 positive cells'pro portion and geometric mean fluorescence.Intestinal bacterial overgrowth were detect ed by Lactobacillus hydrogen breath test(LHBT).According to the LHBT,patients were divided into SIBO-positive group and SIBO-negative group.The serum endot ox were tested by TAL chromogenic substrate Assay(the chromogenic substrate Li mulus amebocyte lysate test).Compared with the TLR2/TLR4 expression,the occurr ence rates of SIBO and the serum levels of among group HBV related hepatocellu lar carcinoma,CHB and control.And the the expression level of TLR2/TLR4 were compared between the group of SIBO positive and SIBO negative.Finally to com pare with the correlation with TLR2/TLR4 expression and endotox in serum levels,respectively.Results1.The positive rate of SIBO in HBV related hepatocellular carcinoma group(71.7%)was significantly higher than that in CHB(28.6%)and healthy volunteers(6.3%)(?~2=14.87,P<?'=0.017;?~2=20.56,P<?'=0.017),and the positive rate of SIBO in CHB group was higher than that in CHB,but there was no statistic difference(P>?'=0.017).2.The expression levels of TLR2 and TLR4(positive cells'proportion and GM F)on peripheral blood CD14~+monocytes in patients with HBV related hepatocellul ar carcinoma were significantly higher than that of CHB patients and healthy contro ls.(70.08?11.83),(76.27?11.13),(94.35?26.05),(41.96?14.32)vs(25.29?7.28),(22.97?7.39),(32.66?7.57),(26.67?5.77)vs(20.83?6.08),(14.89?8.21),(26.96?6.47),(15.21?6.86)(P<0.05);To the proportion of peripheral blood CD14~+monocytes expressi ng TLR2 in patients with CHB,there was no significant difference with healthy con trols(P>0.05).The expression levels of TLR2 positive cells'GMF and TLR4 positi ve cells'proportion and GMF on peripheral blood CD14~+monocytes in patients with CHB were significantly higher than that of healthy controls(P<0.05).3.The expression levels of TLR2 and TLR4(positive cells'proportion and GM F)on peripheral blood CD14~+monocytes are higher in SIBO-positive HBV related hepatocellular carcinoma than that in SIBO-negative patients(73.62?11.10),(80.58?9.00),(103.19?22.75),(46.81?13.90)vs(61.09?11.10),(65.34?8.25),(71.91?20.11),(29.65?4.96)(P<0.05);To the proportion of peripheral blood CD14~+monocytes expressi ng TLR2 and TLR4(positive cells'proportion and GMF)in SIBO-positive CHB pat ients,there was significant difference with SIBO-negative patients(30.85?7.49),(28.15?10.32),(38.24?10.48),(28.15?10.32)vs(23.90?6.65),(21.67?6.03),(31.26?6.13),(24.86?4.76)(P<0.05).4.The endotox level of HBV related hepatocellular carcinoma is apparently high ter than that of group CHB and healthy control(P<0.05).In the endotox lever betwee n SIBO-positive group and SIBO-negative group in HBV related hepatocellular carc inoma,there is siginificant difference statistically(P<0.05).5.TLR2 and TLR4 experssion levels(positive cells'proportion and GMF)were positively correlated with endotox level(r=0.371,r=0.460,r=0.656,r=0.805,P<0.05)in HBV related hepatocellular carcinoma.ConclusionThe incidence of SIBO in HBV related hepatocellular carcinoma patients are si gnificantly higher than that in CHB patients and healthy controls.The expression of TLR2 and TLR4 and endotox level in SIBO-positive patients higher than that in S IBO-negative patients,and TLR2 and TLR4 expression levels were positively correl ated with endotox level.It suggest that SIBO may promote the development of HB V related hepatocellular carcinoma through the high expression of TLR2 and TLR4.
Keywords/Search Tags:HBV related hepatocellular carcinoma, Small intestinal bacteria overgro wth(SIBO), Toll like receptors 2, Toll like receptors 4, endotox
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