脂联素和炎症因子与高尿酸血症的关系及复方土茯苓颗粒的干预

发布时间：2018-04-23 06:43

本文选题：高尿酸血症 + 脂联素　；参考：《广州中医药大学》2017年硕士论文

【摘要】：目的:随着现代经济发展,人们饮食、生活习惯改变,血尿酸升高人群不断增多,由其引发的痛风性关节炎、痛风石及痛风性肾病发病率逐年上升,对人类健康造成巨大危害。近年研究发现,高尿酸血症还与高血糖、高血压、高血脂等代谢性疾病密切相关,并成为代谢综合征的重要组分。有研究表明,高尿酸血症是心血管疾病的独立危险因素。一系列炎症因子和脂肪因子可能是高尿酸血症参与体内代谢紊乱的重要纽带。本研究拟通过观察高尿酸血症患者血清APN、NO及炎症因子MCP-1、TNF-α、IL-6水平的变化及复方土茯苓颗粒干预治疗对其影响,尝试从脂肪因子和炎症因子的角度探讨高尿酸血症发病机理及复方土茯苓颗粒作用机制,为复方土茯苓颗粒防治高尿酸血症提供更充分的理论依据,同时也为降尿酸治疗能否成为防治代谢综合征相关组分提供新思路。方法:第1部分:选取高尿酸血症患者60例,同期选取来自我院体检中心健康体检者36例作为非高尿酸血症组。收集两组临床资料,用ELISA方法检测两组血清APN、MCP-1、IL-6、TNF-α水平,用硝酸还原酶法检测血清NO水平。比较两组指标变化情况,并分析高尿酸血症发病的影响因素、SUA与各指标的相关性及血清APN、MCP-1、NO之间的相关性。第2部分:60例高尿酸血症患者随机分为实验组和对照组各30例。对照组给予健康教育、低嘌呤饮食等生活方式干预;实验组在对照组基础上给予复方土茯苓颗粒10g,水冲服,每日2次。共治疗3个月。比较两组治疗前后SUA、APN、MCP-1、NO、IL-6、TNF-α以及合并代谢性指标的变化。结果:第1部分:1.高尿酸血症与代谢综合征各组分的关系。与非高尿酸组相比较,高尿酸血症组BMI、WC、WHTR、TG、TC水平明显升高(P0.05或P0.01),高尿酸血症合并高血脂、高血压、中心性肥胖及糖尿病比例显著上升(P0.05或P0.01);单变量分析结果显示,SUA与BMI、WHTR、TG、HT、中心性肥胖呈显著相关性,差异有统计学意义(P0.05或P0.01);高尿酸血症合并疾病的二分类回归分析显示,高尿酸血症患者并发中心性肥胖、高血压、高脂血症及高血糖的危险系数分别是非高尿酸组的4.466倍、3.365倍、2.373倍、3.719倍。2.SUA与血清APN的关系。与非高尿酸组相比较,高尿酸血症组血清APN表达量显著降低,差别有统计学意义(P0.01);多变量回归分析结果显示,APN可能是血尿酸的重要影响因素(β=-0.478,P0.01)。3.炎症因子MCP-1、TNF-α、IL-6及NO与高尿酸血症的关系。高尿酸血症患者血清MCP-1、TNF-α、IL-6均较非高尿酸组升高,NO水平较非高尿酸组降低,差异有统计学意义(P0.01或P0.05);单变量分析结果显示,MCP-1、TNF-α 与 SUA 呈正相关(β分别为 0.645、0.217,P0.01 或 P0.05),NO 与 SUA 呈负相关(β=-0.218,P0.01);多变量回归分析结果显示,MCP-1、NO可能是血尿酸的重要影响因素(β分别为0.594、-0.297,P0.05)。4.APN、MCP-1、NO、TNF-α与IL-6之间的相关性。相关性分析结果显示,APN与MCP-1、TNF-α呈负相关(P0.05或P0.01),与NO呈正相关(P0.01);MCP-1 与 NO 呈负相关(P0.05),与 TNF-α 呈正相关(P0.05);TNF-α 与 IL-6呈正相关关系(P0.05)。5.高尿酸血症与肾功能的关系。与非高尿酸组相比,高尿酸血症组Cys C水平显著升高(P0.01),两组血肌酐(CREA)、尿素氮(BUN)比较未发现明显差异(P0.05);单变量分析显示,Cys C与SUA呈正相关(β=0.163,P0.01)。第2部分:1.治疗后两组SUA水平比较。两组SUA水平均较治疗前下降(P0.05或P0.01),实验组SUA水平下降程度明显优于对照组(P0.01)。2.复方土茯苓颗粒对血清APN的影响。与治疗前相比较,实验组治疗后APN显著上升(P0.01),对照组未发现明显变化;实验组较对照组治疗后APN明显上升(P0.01)。3.复方土茯苓颗粒对MCP-1、TNF-α、IL-6、NO的影响。与治疗前相比较,实验组治疗后MCP-1、TNF-α、IL-6表达量均显著下降,NO水平上升(P0.05或P0.01),对照组MCP-1、TNF-α有下降趋势,但无统计学差异;实验组较对照组治疗后MCP-1、TNF-α、IL-6明显下降,NO明显上升(P0.05或P0.01)。4.复方土茯苓颗粒对脂代谢指标的影响。与治疗前相比较,实验组治疗后TG、TC 显著下降(P0.05 或 P0.01),HDL-C 显著上升(P0.01),LDL-C 无明显变化,对照组治疗后上述指标均无明显变化(P0.05);实验组较对照组治疗后TG水平明显下降(P0.05),HDL-C水平明显升高(P0.05)。5.复方土茯苓颗粒对肾功能的影响。治疗后,实验组Cys C水平显著下降,与本组治疗前比较、与对照组比较均有统计学意义(P0.01),两组CREA、BUN治疗前后组内、组间比较无明显变化(P0.05)。结论:1.高尿酸血症与代谢综合征各组分密切相关。高尿酸血症患者体内存在糖脂代谢紊乱,其伴发中心性肥胖的危险性较其他代谢性因素明显升高。2.AP 可能直接或间接参与高尿酸血症的发生发展过程,是尿酸及其他能量代谢的保护因子,可能是高尿酸血症与中心性肥胖关系的中间环节。3.高尿酸血症与炎症因子MCP-1、TNF-α、IL-6及NO密切相关。MCP-1、TNF-α、IL-6可能参与了尿酸诱导的氧化应激反应,NO水平下降是尿酸代谢紊乱的保护因素,提示高尿酸血症是一种慢性低度炎症性疾病,炎症因子参与了高尿酸血症及各种代谢性疾病的发生及病理发展过程,是代谢性疾病之间联系的纽带。4.Cys C可能是尿酸相关性肾病早期肾功能损害的预测指标。炎症因子在其中发挥重要作用。5.复方土茯苓颗粒具有明显的降尿酸作用,可能通过直接或间接上调高尿酸血症患者血清APN、NO水平,下调MCP-1、TNF-α、IL-6水平,改善糖脂代谢紊乱,发挥抗炎、抗氧化应激作用,对高尿酸血症及合并代谢综合征相关组分的一级预防有良好优势。APN水平的升高可能是复方土茯苓颗粒降尿酸及发挥预防代谢性疾病的作用机制之一。6.复方土茯苓颗粒可能通过减少炎症因子表达对肾脏起保护作用。
[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.

【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.7

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