本文選題：高尿酸血癥 + 脂聯(lián)素��； 參考：《廣州中醫(yī)藥大學(xué)》2017年碩士論文

【摘要】：目的:隨著現(xiàn)代經(jīng)濟(jì)發(fā)展,人們飲食、生活習(xí)慣改變,血尿酸升高人群不斷增多,由其引發(fā)的痛風(fēng)性關(guān)節(jié)炎、痛風(fēng)石及痛風(fēng)性腎病發(fā)病率逐年上升,對(duì)人類健康造成巨大危害。近年研究發(fā)現(xiàn),高尿酸血癥還與高血糖、高血壓、高血脂等代謝性疾病密切相關(guān),并成為代謝綜合征的重要組分。有研究表明,高尿酸血癥是心血管疾病的獨(dú)立危險(xiǎn)因素。一系列炎癥因子和脂肪因子可能是高尿酸血癥參與體內(nèi)代謝紊亂的重要紐帶。本研究擬通過(guò)觀察高尿酸血癥患者血清APN、NO及炎癥因子MCP-1、TNF-α、IL-6水平的變化及復(fù)方土茯苓顆粒干預(yù)治療對(duì)其影響,嘗試從脂肪因子和炎癥因子的角度探討高尿酸血癥發(fā)病機(jī)理及復(fù)方土茯苓顆粒作用機(jī)制,為復(fù)方土茯苓顆粒防治高尿酸血癥提供更充分的理論依據(jù),同時(shí)也為降尿酸治療能否成為防治代謝綜合征相關(guān)組分提供新思路。方法:第1部分:選取高尿酸血癥患者60例,同期選取來(lái)自我院體檢中心健康體檢者36例作為非高尿酸血癥組。收集兩組臨床資料,用ELISA方法檢測(cè)兩組血清APN、MCP-1、IL-6、TNF-α水平,用硝酸還原酶法檢測(cè)血清NO水平。比較兩組指標(biāo)變化情況,并分析高尿酸血癥發(fā)病的影響因素、SUA與各指標(biāo)的相關(guān)性及血清APN、MCP-1、NO之間的相關(guān)性。第2部分:60例高尿酸血癥患者隨機(jī)分為實(shí)驗(yàn)組和對(duì)照組各30例。對(duì)照組給予健康教育、低嘌呤飲食等生活方式干預(yù);實(shí)驗(yàn)組在對(duì)照組基礎(chǔ)上給予復(fù)方土茯苓顆粒10g,水沖服,每日2次。共治療3個(gè)月。比較兩組治療前后SUA、APN、MCP-1、NO、IL-6、TNF-α以及合并代謝性指標(biāo)的變化。結(jié)果:第1部分:1.高尿酸血癥與代謝綜合征各組分的關(guān)系。與非高尿酸組相比較,高尿酸血癥組BMI、WC、WHTR、TG、TC水平明顯升高(P0.05或P0.01),高尿酸血癥合并高血脂、高血壓、中心性肥胖及糖尿病比例顯著上升(P0.05或P0.01);單變量分析結(jié)果顯示,SUA與BMI、WHTR、TG、HT、中心性肥胖呈顯著相關(guān)性,差異有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01);高尿酸血癥合并疾病的二分類回歸分析顯示,高尿酸血癥患者并發(fā)中心性肥胖、高血壓、高脂血癥及高血糖的危險(xiǎn)系數(shù)分別是非高尿酸組的4.466倍、3.365倍、2.373倍、3.719倍。2.SUA與血清APN的關(guān)系。與非高尿酸組相比較,高尿酸血癥組血清APN表達(dá)量顯著降低,差別有統(tǒng)計(jì)學(xué)意義(P0.01);多變量回歸分析結(jié)果顯示,APN可能是血尿酸的重要影響因素(β=-0.478,P0.01)。3.炎癥因子MCP-1、TNF-α、IL-6及NO與高尿酸血癥的關(guān)系。高尿酸血癥患者血清MCP-1、TNF-α、IL-6均較非高尿酸組升高,NO水平較非高尿酸組降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01或P0.05);單變量分析結(jié)果顯示,MCP-1、TNF-α 與 SUA 呈正相關(guān)(β分別為 0.645、0.217,P0.01 或 P0.05),NO 與 SUA 呈負(fù)相關(guān)(β=-0.218,P0.01);多變量回歸分析結(jié)果顯示,MCP-1、NO可能是血尿酸的重要影響因素(β分別為0.594、-0.297,P0.05)。4.APN、MCP-1、NO、TNF-α與IL-6之間的相關(guān)性。相關(guān)性分析結(jié)果顯示,APN與MCP-1、TNF-α呈負(fù)相關(guān)(P0.05或P0.01),與NO呈正相關(guān)(P0.01);MCP-1 與 NO 呈負(fù)相關(guān)(P0.05),與 TNF-α 呈正相關(guān)(P0.05);TNF-α 與 IL-6呈正相關(guān)關(guān)系(P0.05)。5.高尿酸血癥與腎功能的關(guān)系。與非高尿酸組相比,高尿酸血癥組Cys C水平顯著升高(P0.01),兩組血肌酐(CREA)、尿素氮(BUN)比較未發(fā)現(xiàn)明顯差異(P0.05);單變量分析顯示,Cys C與SUA呈正相關(guān)(β=0.163,P0.01)。第2部分:1.治療后兩組SUA水平比較。兩組SUA水平均較治療前下降(P0.05或P0.01),實(shí)驗(yàn)組SUA水平下降程度明顯優(yōu)于對(duì)照組(P0.01)。2.復(fù)方土茯苓顆粒對(duì)血清APN的影響。與治療前相比較,實(shí)驗(yàn)組治療后APN顯著上升(P0.01),對(duì)照組未發(fā)現(xiàn)明顯變化;實(shí)驗(yàn)組較對(duì)照組治療后APN明顯上升(P0.01)。3.復(fù)方土茯苓顆粒對(duì)MCP-1、TNF-α、IL-6、NO的影響。與治療前相比較,實(shí)驗(yàn)組治療后MCP-1、TNF-α、IL-6表達(dá)量均顯著下降,NO水平上升(P0.05或P0.01),對(duì)照組MCP-1、TNF-α有下降趨勢(shì),但無(wú)統(tǒng)計(jì)學(xué)差異;實(shí)驗(yàn)組較對(duì)照組治療后MCP-1、TNF-α、IL-6明顯下降,NO明顯上升(P0.05或P0.01)。4.復(fù)方土茯苓顆粒對(duì)脂代謝指標(biāo)的影響。與治療前相比較,實(shí)驗(yàn)組治療后TG、TC 顯著下降(P0.05 或 P0.01),HDL-C 顯著上升(P0.01),LDL-C 無(wú)明顯變化,對(duì)照組治療后上述指標(biāo)均無(wú)明顯變化(P0.05);實(shí)驗(yàn)組較對(duì)照組治療后TG水平明顯下降(P0.05),HDL-C水平明顯升高(P0.05)。5.復(fù)方土茯苓顆粒對(duì)腎功能的影響。治療后,實(shí)驗(yàn)組Cys C水平顯著下降,與本組治療前比較、與對(duì)照組比較均有統(tǒng)計(jì)學(xué)意義(P0.01),兩組CREA、BUN治療前后組內(nèi)、組間比較無(wú)明顯變化(P0.05)。結(jié)論:1.高尿酸血癥與代謝綜合征各組分密切相關(guān)。高尿酸血癥患者體內(nèi)存在糖脂代謝紊亂,其伴發(fā)中心性肥胖的危險(xiǎn)性較其他代謝性因素明顯升高。2.AP 可能直接或間接參與高尿酸血癥的發(fā)生發(fā)展過(guò)程,是尿酸及其他能量代謝的保護(hù)因子,可能是高尿酸血癥與中心性肥胖關(guān)系的中間環(huán)節(jié)。3.高尿酸血癥與炎癥因子MCP-1、TNF-α、IL-6及NO密切相關(guān)。MCP-1、TNF-α、IL-6可能參與了尿酸誘導(dǎo)的氧化應(yīng)激反應(yīng),NO水平下降是尿酸代謝紊亂的保護(hù)因素,提示高尿酸血癥是一種慢性低度炎癥性疾病,炎癥因子參與了高尿酸血癥及各種代謝性疾病的發(fā)生及病理發(fā)展過(guò)程,是代謝性疾病之間聯(lián)系的紐帶。4.Cys C可能是尿酸相關(guān)性腎病早期腎功能損害的預(yù)測(cè)指標(biāo)。炎癥因子在其中發(fā)揮重要作用。5.復(fù)方土茯苓顆粒具有明顯的降尿酸作用,可能通過(guò)直接或間接上調(diào)高尿酸血癥患者血清APN、NO水平,下調(diào)MCP-1、TNF-α、IL-6水平,改善糖脂代謝紊亂,發(fā)揮抗炎、抗氧化應(yīng)激作用,對(duì)高尿酸血癥及合并代謝綜合征相關(guān)組分的一級(jí)預(yù)防有良好優(yōu)勢(shì)。APN水平的升高可能是復(fù)方土茯苓顆粒降尿酸及發(fā)揮預(yù)防代謝性疾病的作用機(jī)制之一。6.復(fù)方土茯苓顆�？赡芡ㄟ^(guò)減少炎癥因子表達(dá)對(duì)腎臟起保護(hù)作用。
[Abstract]:Objective: with the development of modern economy, people's diet and living habits change, the population of blood uric acid is increasing, the incidence of gouty arthritis, gout and gouty nephropathy is increasing year by year, causing great harm to human health. In recent years, the study found that hyperuricemia is also associated with hyperglycemia, hypertension, hyperlipidemia and other metabolic diseases. Diseases are closely related and become important components of metabolic syndrome. Studies have shown that hyperuricemia is an independent risk factor for cardiovascular disease. A series of inflammatory factors and adipose factors may be an important link in hyperuricemia to participate in metabolic disorders in the body. This study is to observe the serum APN, NO and inflammatory factors in patients with hyperuricemia. The changes of MCP-1, TNF- alpha, IL-6 level and the effect of compound tuckaing Granule on the treatment of hyperuricemia, try to explore the pathogenesis of hyperuricemia and the mechanism of compound Smilax glabra from the angle of adipose factors and inflammatory factors, and provide a more sufficient theoretical basis for the prevention and treatment of hyperuricemia by compound Tuckahoe granules, and also for the treatment of uric acid. The first part: 60 cases of hyperuricemia and 36 patients from physical examination in the medical center of our hospital were selected as non hyperuricemia group. Two groups of clinical data were collected, and the levels of serum APN, MCP-1, IL-6, TNF- alpha and nitrate reductase were detected by ELISA method in the two groups. The serum NO level was measured and the changes of the two groups were compared, the factors affecting the incidence of hyperuricemia, the correlation between SUA and the indexes and the correlation between the serum APN, MCP-1, NO were analyzed. The second part: 60 cases of hyperuricemia were randomly divided into the experimental group and the control group (30 cases each). The control group was given health education, low purine diet and other life. In the control group, the experimental group was given the compound tuckahoe granule 10g on the basis of the control group. The water was washed 2 times a day for 3 months. The changes of SUA, APN, MCP-1, NO, IL-6, TNF- A and the metabolic indices before and after the treatment were compared between the two groups. Results: the first part: the relationship between 1. high uric acid blood syndrome and the components of metabolic syndrome. Compared with hyperuricemia, the levels of BMI, WC, WHTR, TG and TC were significantly increased (P0.05 or P0.01). The proportion of hyperuricemia with hyperlipidemia, hypertension, central obesity and diabetes increased significantly (P0.05 or P0.01). The results of univariate analysis showed that SUA and BMI, WHTR, and obesity were significantly correlated. The two classification regression analysis of hyperuricemia with disease showed that the risk factors of central obesity, hypertension, hyperlipidemia and hyperglycemia in hyperuricemia patients were 4.466 times, 3.365 times, 2.373 times, 3.719 times.2.SUA and serum APN, respectively. Compared with the non high uric acid group, the serum APN table of hyperuricemia group was compared with the non high uric acid group. The difference was statistically significant (P0.01). The results of multivariate regression analysis showed that APN may be an important factor of the blood uric acid (beta =-0.478, P0.01).3. inflammatory factor MCP-1, TNF- a, IL-6 and NO and hyperuricemia. The serum MCP-1, TNF- alpha, IL-6 were higher than non high uric acid group, and the level was not high The difference in uric acid group was statistically significant (P0.01 or P0.05); the results of single variable analysis showed that MCP-1 and TNF- alpha were positively correlated with SUA (beta 0.645,0.217, P0.01 or P0.05, respectively), and NO and SUA were negatively correlated (beta =-0.218, P0.01). -0.297, P0.05) the correlation between.4.APN, MCP-1, NO, TNF- alpha and IL-6. Correlation analysis showed that APN and MCP-1, TNF- alpha were negatively correlated (P0.05 or P0.01). Relationship. Compared with the non high uric acid group, the level of Cys C in the hyperuricemia group increased significantly (P0.01), the two groups of serum creatinine (CREA) and urea nitrogen (BUN) were not significantly different (P0.05). The single variable analysis showed that Cys C and SUA were positively correlated (Beta =0.163, P0.01). Second parts were compared with the 1. groups after treatment. The two groups were all lower than those before the treatment. 5 or P0.01), the level of SUA in the experimental group was obviously superior to that of the control group (P0.01). The effect of.2. compound Smilax Granule on serum APN was significantly higher than that before treatment (P0.01) in the experimental group (P0.01), and in the control group, no obvious change was found in the control group; the experimental group was significantly higher than the control group after the treatment (P0.01).3. compound Smilax glabra granules to MCP-1, TNF- The effect of alpha, IL-6 and NO. Compared with before treatment, the expression of MCP-1, TNF- a, IL-6 in the experimental group decreased significantly, the level of NO increased (P0.05 or P0.01), the control group was MCP-1, TNF- a decreased, but there was no statistical difference. The experimental group was significantly lower than the control group. The effect of particle on lipid metabolism index was compared with that before treatment. After treatment, TG, TC decreased significantly (P0.05 or P0.01), HDL-C increased significantly (P0.01), LDL-C had no obvious changes, no significant changes were observed in the control group (P0.05) after treatment (P0.05), and the level of HDL-C was significantly increased (P0.) in the experimental group (P0.05) and HDL-C level (P0.). 05) the effect of.5. compound tuckahoe Granule on renal function. After treatment, the level of Cys C in the experimental group decreased significantly, compared with the control group before treatment, compared with the control group, there was significant difference (P0.01). There was no significant change between the two groups of CREA and BUN before and after treatment (P0.05). Conclusion: 1. hyperuricemia is closely related to the components of metabolic syndrome. The metabolic disorder of glycolipidemia in patients with uric acid, which is more dangerous than other metabolic factors, may be directly or indirectly involved in the development of hyperuricemia, and it is a protective factor for uric acid and other energy metabolism. It may be the middle ring of the relationship between hyperuricemia and central obesity. .3. hyperuricemia is closely related to inflammatory factors MCP-1, TNF- a, IL-6 and NO,.MCP-1, TNF- a, IL-6 may be involved in the oxidative stress induced by uric acid. The decrease of NO level is a protective factor for uric acid metabolism disorder. It suggests that hyperuricemia is a chronic low inflammatory disease, and inflammatory factors are involved in hyperuricemia and various metabolism. The occurrence and pathological process of sexual disease is the link between metabolic diseases,.4.Cys C may be a predictor of early renal impairment in uric acid related nephropathy. The inflammatory factors play an important role in.5. compound soil Poria granules, which have obvious effect on reducing uric acid, which can be directly or indirectly up-regulated in hyperuricemia patients. Serum APN, NO level, down regulation of MCP-1, TNF- a, IL-6 level, improve the metabolic disorder of glycolipid, exert anti-inflammatory and anti oxidative stress, and increase the level of.APN in the primary prevention of hyperuricemia and associated components of metabolic syndrome, may be the effect mechanism of compound Smilax glabra Granule on uric acid and preventing metabolic disease One of the.6. compound tuckahoe granules may protect the kidneys by reducing the expression of inflammatory factors.

【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R589.7

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