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The Analysis Of Related Risk Factors In Patients With Gout And The Expression Of Inflammatory Cytokines In Peirpheral Blood

Posted on:2014-11-12Degree:MasterType:Thesis
Country:ChinaCandidate:L L HeFull Text:PDF
GTID:2254330398966646Subject:Internal medicine
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Backgrounds and objectives:gout is a kind of inflammation disease caused byurate crystals depositing in and around the joints. It is clinically characterized by goutyarthritis, tophi, uric acid kidney stones and gouty kidney diseases. Gouty arthritis is thesymptom of first flare, which is also the commonest inflamed arthritis among the malewho is aged over40. Study showed that gout is strongly linked to hypertension,hyperlipidemia, atherosclerosis, obesity and insulin resistance and so on, which is anindependent dangerous factor of cardiovascular diseases. In the past five years, the basicresearch, clinical diagnosis and treatment development of gout are under explorationand have made progress. Nowadays, increased uric acid levels in the blood may lead togout attack; however, only5%~12%of hyperuricemia patients will develop to gout. Itwas clinically found that blood uric acid level is not high among some acute goutyarthritis patients; moreover, gout was not flared frequently among some patients havingmany tophus. Typical clinical symptoms of gout make it diagnosed easily, but somenon-typical gout may be misled to diagnose. Some studies are helpful to prevent anddiagnose gout, such as the part of arthritis first flare, reference value of blood uric acidand dangerous factors of gout.Since1960s, Faires and MacCarty have proved that MSU is strongly linked to goutbased on a research that MSU was injected to dogs’ joints, which led to acuteinflammation due to the infiltration of neutrophils, but the principle of which isunknown. A few hyperuricemia patients develop to gout even if increased blood uricacid is the basic factor for gout, which might be related to body conditions; such asdropping temperature and PH value, over-saturated due to water re-absorbing, uratecrystals depositing in the joints and soft tissues, trauma and tissue lesion, change ofConnective tissue matrix. Recently, some researches showed that gouty arthritisinflammation attacked by urate crystals is related closely to immune abnormality, inwhich NALP3plays a significant role. Furthermore, NALP3has been proved torecognize the urate crystals released by apoptosis cells, which will active NALP3inorder to push IL-1β and IL-18mature and secretion, thus leads to inflammation.However, its pathogenesis is unsure.The purpose of this study is to help diagnosis of non-typical gout through analysisof joints’ characteristics for first flare. Meanwhile, patients’ vital signs (height, weight and BP), hematology and blood chemistry should be measured and recorded in order toanalyze gout attack factors through comparing with healthy controlled group, finally tointerfere in advanced patients. Based on the measurement of ELISA, the expression ofNALP3, ASC, Caspase-1, IL-1β and IL-18in the blood of acute/chronic gout subjectsand controlled healthy subjects will help to analyze the inflammation characteristics inacute and chronic gout attacks in order to have a clear picture of their functions andinflammatory markers of acute gout. Moreover, it will provide evidences to treattargeted gout.Methods:Based on case-control study to analyze gout related dangerous factors,the data of72acute gout patients and83chronic ones was collected from in orout-patients in the rheumatic department of some Tertiary Hospital during April2012toJanuary2013. The controlled group was80healthy subjects without gout or otherrelated diseases from same hospital with matched gender and age. Collecting gender,age, height, weight and some information of first flare; collecting blood samples for thetest of hematology and chemistry; entering to Excel form based on data management.Logistic regression analysis gout risk factors using statistical software SPSS18.0. Acuteand chronic gout patients expression of inflammatory cytokines by collecting peripheralblood in each group patients. Acute and chronic gout patients expression ofinflammatory cytokines in peripheral blood through collection of patients in each group,using ELISA detection, the data input SPSS18.0statistical software Graphpad prism5software for single-factor analysis of variance and statistical results diagramming.Results: This study includes155patients with gout,80healthy people ascompared group, the age and gender of the people in the two groups are matched eachother. Most of the patients with gout are male and the male to female ratio is18.4:1.1. The characteristics of the first gouty joint and the analysis of related risk factorsThe first gouty joints are listed successively as follows: metatarsophalangeal joints(including the first and the third metatarsophalangeal joint), ankle joint, knee joint,articulatio carpi, articulationes manus and so on. The percentage is75.48%,14.19%,5.81%,3.87%, and0.65%respectively. The result of single factor analysis shows thatgout has potential correlation with cholesterol total, triglyceride, high densitylipoprotein cholesterol, low density lipoprotein cholesterol, height and weight index,blood glucose, uric acid and creatinine respectively.(p<0.05). Further analysis usedmulti-factors Logistic regression method shows that a high level of triglyceride, bloodglucose, creatinine and uric acid are risk factors of gout.(p<0.01). The low level of high density lipoprotein cholesterol is also a risk factor of gout compared to the normallevel. There is no statistical significance of the low level of high density lipoproteincholesterol compared to the normal level.(p>0.05)2. The study expression of inflammatory factors in peripheral blood of patient withacute and chronic gouty arthritis.(1) There is no statistical significance of difference of NALP3in serum betweenacute gouty arthritis, chronic gouty arthritis and healthy group (p>0.05), mean±standarderror is (3.34±0.36) ng/ml,(3.30±0.27) ng/ml,(3.38±0.32) ng/ml respectively.(2) In the three groups, Caspase-1in serum of acute gouty arthritis group is higherthan chronic gouty arthritis group and both of the two groups are higher than the healthygroup. There is statistical significance between each of them,(p<0.05). mean±standarderror is (63.52±15.13)umol/L,(59.02±10.05) umol/L,(52.68±11.72) umol/L respectively.(3) ASC in serum of acute and chronic gouty arthritis group are both higher thanhealthy group, the differences have statistical significance,(p<0.05).There is statisticalsignificance of difference between acute gouty arthritis group and chronic goutyarthritis group,(P=0.029). mean±standard error is (6.95±4.83) ng/ml,(8.08±2.04)ng/ml,(5.88±2.07) ng/ml respectively.(4) IL-18in serum of acute gouty arthritis group is higher than chronic goutyarthritis group and healthy group. The differences have statistical significance.(p<0.001)The chronic gouty arthritis group is lower than healthy group but the difference has nostatistical significance.(p>0.05) mean±standard error is (94.82±64.05)pg/ml,(62.45±19.84) pg/ml,(62.00±19.22) pg/ml respectively.(5) IL-1β in serum of acute and chronic gouty arthritis group are both lower thanhealthy group, the differences have statistical significance,(p<0.01). The acute goutyarthritis group is lower than chronic gouty arthritis group but the difference has nostatistical significance,(p>0.05). mean±standard error is (277.05±125.46)pg/ml,(295.±60.13) pg/ml,(339.43±86.07)pg/ml respectively.Conclusion: Gout is mainly found in male, the first gouty joints are listedsuccessively as follows: metatarsophalangeal joints (including the first and the thirdmetatarsophalangeal joint), ankle joint, knee joint, articulatio carpi and articulationesmanus. High triglyceride, blood glucose, creatinine and uric acid are four independentrisk factors of gout. Compared to the normal group, the low level of high densitylipoprotein cholesterol is also a risk factor of gout. There is no statistical significance Caspase-1and ASC as three inflammatory factors have all token part in the procedure ofgout occurring. IL-18, Caspase-1can be used as inflammatory signs for gout acuteoccurring, but the inflammatory factor of ASC is only token part in the procedure ofgout occurring, it can not be used as inflammatory sign for gout acute occurring. IL-1βis also token part in the procedure of gout occurring, but there may be many influencefactors, so it can not be used as inflammatory sign for gout acute occurring.
Keywords/Search Tags:gout, Hyperlipidemia, IL-18, ASC, Caspase-1
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