本文關(guān)鍵詞： 高尿酸血癥 痛風(fēng) 內(nèi)皮功能 炎癥因子 腎素-血管緊張素系統(tǒng)　出處：《北京協(xié)和醫(yī)學(xué)院》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：背景 尿酸是嘌呤代謝產(chǎn)物,人類進(jìn)化過程中尿酸酶基因突變,使人的血尿酸水平較其它哺乳動物高。高尿酸血癥和痛風(fēng)的患病率呈逐年上升趨勢,臨床觀察到高尿酸血癥與心血管疾病有密切聯(lián)系,除此之外在慢性腎臟疾病患者中高尿酸血癥也不少見。盡管很早人們就發(fā)現(xiàn)血清高濃度尿酸可作為心血管疾病危險性的標(biāo)志,但兩者之間的沒有得出確切的因果關(guān)聯(lián)。高尿酸血癥和此類疾病之間的病理生理基礎(chǔ)或許是內(nèi)皮功能和炎癥水平的變化。但是尿酸在這其中發(fā)揮的作用卻存在一定分歧。 目的 1)通過建立痛風(fēng)門診數(shù)據(jù)庫分析本院痛風(fēng)患者的臨床特點(diǎn)；2)分析痛風(fēng)患者內(nèi)皮功能水平和降尿酸治療后痛風(fēng)患者的內(nèi)皮功能變化；3)觀察高尿酸血癥大鼠和痛風(fēng)患者血管內(nèi)皮功能和內(nèi)皮腎素-血管緊張素系統(tǒng)(renin-angiotensin system,RAS)的變化。 方法 1.1)2008年1月到2012年2月間就診于北京協(xié)和醫(yī)院普通內(nèi)科痛風(fēng)門診的358例痛風(fēng)患者,填寫調(diào)查問卷,收集人口學(xué)、病史、痛風(fēng)石、既往生活方式、發(fā)作誘因、腎結(jié)石和合并疾病等資料；并進(jìn)行體格檢查和實(shí)驗(yàn)室檢查,將以上資料錄入痛風(fēng)門診數(shù)據(jù)庫系統(tǒng)并進(jìn)行數(shù)據(jù)導(dǎo)出和分析。2)對就診于北京協(xié)和醫(yī)院普通內(nèi)科痛風(fēng)門診的33例痛風(fēng)患者和在我院進(jìn)行健康查體的31例高尿酸血癥患者進(jìn)行人口學(xué)資料、病史、合并疾病、合并用藥詢問,進(jìn)行體格檢查和實(shí)驗(yàn)室檢查,E1ISA法測試血清TNF-α、sICAM-1。對痛風(fēng)患者進(jìn)行28周降尿酸治療,評價TNF-α、sICAM-1水平變化。3)使用2%的氧嗪酸飼料和100umol/L的尿酸水,后增加氧嗪酸灌胃的方法建立長期高尿酸血癥動物模型,對高尿酸大鼠和痛風(fēng)患者血管內(nèi)皮eNOS、ICAM、ACE和Ang-Ⅱ進(jìn)行免疫組化染色尋找血管損傷和RAS激活的證據(jù)。 結(jié)果 1)男性350例(97.8%),女性8例(2.2%),年齡46±13歲,平均病程99月,多關(guān)節(jié)受累多見,占78.4%,血清尿酸586±123μmol/L.77例患者(21.5%)發(fā)現(xiàn)痛風(fēng)石,logistic回歸顯示尿酸水平和病程與痛風(fēng)石的發(fā)生相關(guān)(P0.001),256例(71.5%)合并基礎(chǔ)疾病,基礎(chǔ)疾病的合并存在與高齡相關(guān)(P0.001)。青年組病程較中老年組短(P0.01),尿酸水平高于中老年組(P0.05),秩和檢驗(yàn)結(jié)果顯示累計(jì)關(guān)節(jié)數(shù)方面兩組無統(tǒng)計(jì)學(xué)差異(P0.05)；中老年基礎(chǔ)疾病合并率較青年組高(P0.01)。2)痛風(fēng)患者組舒張壓高于高尿酸血癥組；痛風(fēng)患者組血尿酸水平、TNF-α和sICAM水平高于高尿酸血癥組,差異有統(tǒng)計(jì)學(xué)意義。年齡、BMI、收縮壓、HDL-C、LDL-C、TC、TG、GFR、Cr和Glu差異無統(tǒng)計(jì)學(xué)意義。Logistic回歸結(jié)果顯示痛風(fēng)和sICAM顯著相關(guān)。別嘌醇、非布司他40mg和80mg能顯著降低痛風(fēng)患者的尿酸水平,其中80mg療效次于前兩者,可能與患者的病程和尿酸水平相關(guān)。中國人非布司他應(yīng)盡量從小劑量用起。剔除兩次隨訪期間有發(fā)作的患者后,降尿酸治療后TNF-α和s-ICAM水平下降。3)高尿酸血癥模型大鼠腎內(nèi)局部ICAM表達(dá)增強(qiáng),經(jīng)別嘌醇處理后盡管ICAM水平有所降低,但無統(tǒng)計(jì)學(xué)意義。Ang-Ⅱ在高尿酸血癥大鼠模型中和痛風(fēng)組患者中有表達(dá)增強(qiáng)。 結(jié)論 1)痛風(fēng)患者的臨床特征更具多樣化、復(fù)雜化,表現(xiàn)為病程較長,痛風(fēng)石受累多見,多關(guān)節(jié)受累多見,非典型關(guān)節(jié)受累并不罕見,基礎(chǔ)疾病合并率高,腎損傷多見。痛風(fēng)在發(fā)病率普遍提高的同時,臨床特點(diǎn)也發(fā)生著變化。積極早期控制痛風(fēng)的可逆性危險因素如肥胖、飲酒、高嘌呤飲食、藥物可使更多的患者從中獲益,減少重癥難治性痛風(fēng),關(guān)節(jié)致殘,痛風(fēng)腎病的發(fā)生,改善患者的生活質(zhì)量和預(yù)后。近年來,青年痛風(fēng)患者發(fā)病也呈上升趨勢,需特別關(guān)注這一人群的關(guān)節(jié)和合并的臨床問題,積極尋找可控制的因素并針對以上因素加以管理。2)痛風(fēng)患者相對于無癥狀高尿酸血癥TNF-α水平s-ICAM水平有所增高,但僅血尿酸和sICAM獨(dú)立相關(guān)。降尿酸治療可有效改善內(nèi)皮功能和炎癥狀態(tài)。3)提示尿酸存在對大鼠腎臟內(nèi)皮功能損傷作用和局部RAS激活作用；尿酸可明顯激活痛風(fēng)患者血管內(nèi)皮RAS,可能機(jī)制包括為非ACE途徑。
[Abstract]:background
Uric acid is a product of purine metabolism, uricase gene mutation in human evolution, so that the blood uric acid level of people than other mammals. The prevalence of gout and hyperuricemia increased year by year, the clinical observation of hyperuricemia is closely related to cardiovascular disease, besides hyperuricemia in patients with chronic kidney disease is not uncommon. Although it is as early as it was found that high serum uric acid as a marker for cardiovascular disease risk, but they did not draw the exact causal association between hyperuricemia and disease. This disease may be the physiological basis of physical changes of endothelial function and inflammation levels. But uric acid play role in this but there are some differences.
objective
1) by analyzing the clinical characteristics of gout patients in our hospital to establish gout out-patient database; 2) analysis of the level of endothelial function in patients with gout and uric acid after treatment of endothelial function in patients with gout change; 3) were observed in rats with hyperuricemia and gout in patients with vascular endothelial function and endothelial renin-angiotensin system (renin-angiotensin, system, RAS) changes.
Method
1.1) 358 cases of gout patients from January 2008 to February 2012 in Peking Union Medical College Hospital from general medical outpatient gout, fill in the questionnaire to collect demographic, medical history, history of tophi, lifestyle, inducement, data of kidney stones and complications; and physical examination and laboratory examination, the data of database system and gout clinic export data and analysis.2) 33 cases of gout patients admitted to Peking Union Medical College Hospital outpatient and general medical gout in our hospital 31 cases of patients with hyperuricemia health examination of demographic data, medical history, concomitant diseases, medication enquiry, physical examination and laboratory test, serum TNF- E1ISA alpha, sICAM-1. gout patients 28 weeks of urate lowering therapy, evaluation of TNF- alpha,.3 changes in sICAM-1 levels) using 2% oxonate feed and 100umol /L acid water, then increased A long-term hyperuricemia animal model was established by intragastric administration of oxazine. Immunohistochemical staining of eNOS, ICAM, ACE and Ang- II in vascular endothelial cells of hyperuricemia rats and gout patients was performed to detect the evidence of vascular injury and RAS activation.
Result
1) male 350 cases (97.8%), 8 cases of female (2.2%), age 46 + 13 years old, the average duration of 99 months, multiple joint involvement was more common, accounting for 78.4%, 586 + 123 mol/L.77 of serum uric acid in patients (21.5%) found tophi, logistic regression analysis showed that uric acid level and the course of disease and gout. Students (P0.001), 256 cases (71.5%) with basic diseases, and age related with basic diseases (P0.001). The youth group course is in the elderly group (P0.01), short of uric acid is higher than that of the elderly group (P0.05), rank sum test results show that the total number of joint (no significant difference between two groups P0.05); in the elderly compared with young group based disease with high rate of (P0.01).2) in patients with gout group diastolic pressure was higher in hyperuricemia group; group of blood uric acid in patients with gout, TNF- and sICAM levels were higher than that in hyperuricemia group, the difference was statistically significant. The age, systolic blood pressure, BMI, HDL-C, LDL-C, TC, TG, GFR Cr, and the difference of Glu No statistical significance of.Logistic regression showed significant correlation of gout and sICAM. Allopurinol, febuxostat 40mg and 80mg can significantly reduce the level of uric acid in patients with gout, including the effect of 80mg to the first two, may be associated with disease related and uric acid levels. Chinese febuxostat should be small dose used. The onset of patients during follow-up after excluding two, down.3 TNF- alpha and s-ICAM levels of uric acid after treatment) enhanced the expression of hyperuricemia rat model of kidney in the local ICAM, by allopurinol treatment while the ICAM level decreased, but there was no statistical significance of.Ang- II expression in hyperuricemia rat model and gout patients.
conclusion
1) the clinical features of patients with gout are more diverse, complex, showed a longer course of disease, gout involvement was more common, multiple joint involvement, atypical joint involvement is not uncommon, basic disease with high rate of kidney injury. A general increase in the incidence of gout and clinical features are also changing. The reversible risk factors of early active control gout such as obesity, alcohol consumption, high purine diet, drugs can make more patients benefit from less severe refractory gout, joint disability, gout nephropathy, improve life quality and prognosis of the patients. In recent years, the incidence of young patients with gout is also on the rise. Clinical problems need special attention of this group of joint and combined, actively looking for the control factors and management of.2 in view of the above factors) asymptomatic hyperuricemia TNF- alpha level of s-ICAM levels increased compared to patients with gout , but only the blood uric acid and sICAM independently. Urate lowering therapy can effectively improve endothelial function and inflammation.3) suggest that uric acid activation on renal endothelial function injury in rats and the local RAS; uric acid can obviously activate vascular endothelial RAS in patients with gout, including possible mechanism for non ACE way.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R363

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