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尿酸對非酒精性脂肪性肝病肝臟病變的影響

發(fā)布時(shí)間:2018-05-02 14:34

  本文選題:尿酸 + 非酒精性脂肪性肝病 ; 參考:《大連醫(yī)科大學(xué)》2016年碩士論文


【摘要】:第一部血清尿酸與非酒精性脂肪性肝病患者肝臟損傷相關(guān)性研究目的:探討血清尿酸與非酒精性脂肪性肝病患者(NAFLD)肝臟損傷的關(guān)聯(lián)。方法:選擇杭州市西溪醫(yī)院和杭州師范大學(xué)附屬醫(yī)院共約3792例體檢者,檢測其人體學(xué)指標(biāo)、生化指標(biāo);選取280例行Fibroscan檢測的NAFLD患者,檢測其肝臟彈性值、人體學(xué)指標(biāo)、生化指標(biāo);選取191例行肝組織病理學(xué)檢查的NAFLD患者,檢測其人體學(xué)指標(biāo)、生化指標(biāo)、肝臟組織病理學(xué)指標(biāo)。結(jié)果:體檢人群中NAFLD患者占38.4%(1456/3792);NAFLD患者的血清尿酸水平顯著高于正常對照組(353.4±90.2umol/l vs.295.0±86.3umol/l,p0.05);Pearson相關(guān)分析顯示,尿酸與身高體重指數(shù)(BMI)、膽固醇(TG)、甘油三酯(TC)、谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)、谷氨酰轉(zhuǎn)肽酶(GGT)、血清肌苷(SCr)、尿素氮(BUN)、低密度脂蛋白(LDL-c)呈正相關(guān),而與高密度脂蛋白(HDL-c)呈負(fù)相關(guān);Logistic多因素回歸分析顯示高尿酸血癥是非酒精性脂肪性肝病的一個獨(dú)立危險(xiǎn)因素(OR:1.903,95%CI:1.526-2.347;p0.05);280例行Fibroscan檢測的NAFLD患者中,ALT升高組的血清尿酸水平明顯高于ALT正常組,有顯著性差異(p0.05);進(jìn)展性肝纖維化組和對照組的血清尿酸水平無顯著性差異(p0.05);191例行肝組織病理學(xué)檢查的NAFLD患者中,高尿酸血癥組的非酒精性脂肪性肝病活動度積分(NAS)評分顯著高于尿酸正常組,同時(shí)高尿酸血癥組的脂肪變評分較尿酸正常組嚴(yán)重,有顯著性差異(p0.05),而纖維化分期無顯著性差異(p0.05)。結(jié)論:高尿酸血癥是非酒精性脂肪性肝病的一個獨(dú)立危險(xiǎn)因素,高尿酸血癥與NAFLD患者肝臟炎癥進(jìn)展相關(guān)。第二部高尿酸血癥對NAFLD大鼠肝臟病變的影響目的:建立一種持久穩(wěn)定的非酒精性脂肪性肝病合并高尿酸血癥的大鼠模型;探討高尿酸血癥對NAFLD大鼠肝臟病變的影響。方法:選取90只8周齡SPF級雄性SD大鼠,適應(yīng)性喂養(yǎng)1周后隨機(jī)分為3組:普通飲食組、高脂飲食組、高脂高酵母飲食組。每2周監(jiān)測大鼠肝功能(ALT、AST)、血脂(TG、TC)、血尿酸(UA)等生化指標(biāo)水平。第8周開始,高脂高酵母飲食組分2次皮下注射氧嗪酸鉀乳懸液100 mg/(kg*d);普通飲食組和高脂飲食組均予以相同劑量的生理鹽水皮下注射,并繼續(xù)監(jiān)測以上生化指標(biāo)。第3、7、11周末分別處死一批大鼠,行肝組織病理學(xué)檢查。結(jié)果:實(shí)驗(yàn)第3周開始,高脂高酵母組尿酸(UA)、膽固醇(TC)、甘油三酯(TG)水平顯著高于正常對照組(P0.05),第7周時(shí)肝臟組織病理學(xué)顯示高脂高酵母飲食組和高脂飲食組均出現(xiàn)肝脂肪變、小葉內(nèi)炎癥,第11周時(shí)高脂高酵母飲食組較高脂飲食組NAS積分更高,小葉內(nèi)炎癥更重。結(jié)論:以高脂高酵母飼料聯(lián)合腺嘌呤灌胃并適時(shí)皮下注射氧嗪酸鉀乳懸液可建立持久穩(wěn)定的高尿酸血癥合并非酒精性脂肪性肝病的大鼠模型;血清尿酸水平升高與NAFLD肝臟炎癥的進(jìn)展相關(guān)。
[Abstract]:The relationship between serum uric acid and liver injury in patients with non-alcoholic fatty liver disease objective: to investigate the relationship between serum uric acid and NAF LDD liver injury in patients with non-alcoholic fatty liver disease. Methods: a total of 3792 physical examiners were selected from Xixi Hospital of Hangzhou and affiliated Hospital of Hangzhou normal University to detect their ergonomic and biochemical indexes, and to detect the liver elasticity and ergonomic indexes of 280 NAFLD patients who were examined by Fibroscan. Biochemical indexes: NAFLD patients who underwent liver histopathological examination were selected and their anthropometric, biochemical and hepatic histopathological indexes were detected. Results: the serum uric acid level in the patients with NAFLD was significantly higher than that in the normal control group (353.4 鹵86.3 umol / L P 0.05), and the correlation analysis showed that the level of serum uric acid in the patients with NAFLD was significantly higher than that in the normal control group (P < 0.05), and the level of serum uric acid in the patients with NAFLD was significantly higher than that in the normal control group (P < 0.05). There was a positive correlation between uric acid and body mass index (BMI), cholesterol TGG, triglyceride TCU, alanine aminotransferase (alt), aspartate aminotransferase (AST), glutamyl transpeptidase (GGTN), serum inosine trinosine, urea nitrogen bun, low density lipoprotein (LDL-c). Logistic multivariate regression analysis showed that hyperuricemia was an independent risk factor for non-alcoholic fatty liver disease with high density lipoprotein (HDL-c). It was significantly higher than that in the normal ALT group. There was no significant difference in serum uric acid level between progressive hepatic fibrosis group and control group. The activity score of non-alcoholic fatty liver disease in hyperuricemia group was significantly higher than that in normal uric acid group, and the steatosis score in hyperuricemia group was more serious than that in normal uric acid group (p 0.05), but there was no significant difference in fibrosis stage (P 0.05). Conclusion: hyperuricemia is an independent risk factor for nonalcoholic fatty liver disease. Hyperuricemia is associated with the progression of hepatic inflammation in patients with NAFLD. The effect of hyperuricemia on hepatic lesions in NAFLD rats objective: to establish a stable model of non-alcoholic fatty liver disease with hyperuricemia and to explore the effect of hyperuricemia on hepatic lesions in NAFLD rats. Methods: ninety 8-week-old SPF male SD rats were randomly divided into three groups: general diet group, high-fat diet group and high-fat high-yeast diet group. The liver function of rats was monitored every 2 weeks, and the levels of alt, TGG, UAA and TGG were measured. From the 8th week, the high-fat high-yeast diet group was subcutaneously injected with 100 mg / kg of oxazinate potassium milk suspension, and the normal saline was subcutaneously injected into the normal diet group and the high-fat diet group, and the above biochemical indexes were continuously monitored. One group of rats were killed at the end of the 11th week of the third week, and the liver histopathology was performed. Results: from the third week of the experiment, the levels of uric acid, cholesterol, triglyceride and TGin in the hyperlipidemia and high yeast group were significantly higher than those in the normal control group (P 0.05). At the 7th week, liver histopathology showed that both the high fat yeast diet group and the high fat diet group had hepatic fat change. In the 11th week, the NAS score of high-fat high-yeast diet group was higher than that of high-fat diet group, and the intralobular inflammation was more serious than that of high-fat diet group. Conclusion: hyperuricemia with hyperuricemia combined with non-alcoholic fatty liver disease can be established by hyperlipidemia combined with adenine intragastric perfusion and timely subcutaneous injection of potassium oxazinate milk suspension. Elevated serum uric acid levels are associated with the progression of liver inflammation in NAFLD.
【學(xué)位授予單位】:大連醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2016
【分類號】:R575

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 張培;苗志敏;李長貴;牛佳鵬;;慢性高尿酸血癥大鼠模型建立方法的探討[J];青島大學(xué)醫(yī)學(xué)院學(xué)報(bào);2010年03期



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