尿酸对非酒精性脂肪性肝病肝脏病变的影响

发布时间：2018-05-02 14:34

本文选题：尿酸 + 非酒精性脂肪性肝病　；参考：《大连医科大学》2016年硕士论文

【摘要】：第一部血清尿酸与非酒精性脂肪性肝病患者肝脏损伤相关性研究目的:探讨血清尿酸与非酒精性脂肪性肝病患者(NAFLD)肝脏损伤的关联。方法:选择杭州市西溪医院和杭州师范大学附属医院共约3792例体检者,检测其人体学指标、生化指标;选取280例行Fibroscan检测的NAFLD患者,检测其肝脏弹性值、人体学指标、生化指标;选取191例行肝组织病理学检查的NAFLD患者,检测其人体学指标、生化指标、肝脏组织病理学指标。结果:体检人群中NAFLD患者占38.4%(1456/3792);NAFLD患者的血清尿酸水平显著高于正常对照组(353.4±90.2umol/l vs.295.0±86.3umol/l,p0.05);Pearson相关分析显示,尿酸与身高体重指数(BMI)、胆固醇(TG)、甘油三酯(TC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、血清肌苷(SCr)、尿素氮(BUN)、低密度脂蛋白(LDL-c)呈正相关,而与高密度脂蛋白(HDL-c)呈负相关;Logistic多因素回归分析显示高尿酸血症是非酒精性脂肪性肝病的一个独立危险因素(OR:1.903,95%CI:1.526-2.347;p0.05);280例行Fibroscan检测的NAFLD患者中,ALT升高组的血清尿酸水平明显高于ALT正常组,有显著性差异(p0.05);进展性肝纤维化组和对照组的血清尿酸水平无显著性差异(p0.05);191例行肝组织病理学检查的NAFLD患者中,高尿酸血症组的非酒精性脂肪性肝病活动度积分(NAS)评分显著高于尿酸正常组,同时高尿酸血症组的脂肪变评分较尿酸正常组严重,有显著性差异(p0.05),而纤维化分期无显著性差异(p0.05)。结论:高尿酸血症是非酒精性脂肪性肝病的一个独立危险因素,高尿酸血症与NAFLD患者肝脏炎症进展相关。第二部高尿酸血症对NAFLD大鼠肝脏病变的影响目的:建立一种持久稳定的非酒精性脂肪性肝病合并高尿酸血症的大鼠模型;探讨高尿酸血症对NAFLD大鼠肝脏病变的影响。方法:选取90只8周龄SPF级雄性SD大鼠,适应性喂养1周后随机分为3组:普通饮食组、高脂饮食组、高脂高酵母饮食组。每2周监测大鼠肝功能(ALT、AST)、血脂(TG、TC)、血尿酸(UA)等生化指标水平。第8周开始,高脂高酵母饮食组分2次皮下注射氧嗪酸钾乳悬液100 mg/(kg*d);普通饮食组和高脂饮食组均予以相同剂量的生理盐水皮下注射,并继续监测以上生化指标。第3、7、11周末分别处死一批大鼠,行肝组织病理学检查。结果:实验第3周开始,高脂高酵母组尿酸(UA)、胆固醇(TC)、甘油三酯(TG)水平显著高于正常对照组(P0.05),第7周时肝脏组织病理学显示高脂高酵母饮食组和高脂饮食组均出现肝脂肪变、小叶内炎症,第11周时高脂高酵母饮食组较高脂饮食组NAS积分更高,小叶内炎症更重。结论:以高脂高酵母饲料联合腺嘌呤灌胃并适时皮下注射氧嗪酸钾乳悬液可建立持久稳定的高尿酸血症合并非酒精性脂肪性肝病的大鼠模型;血清尿酸水平升高与NAFLD肝脏炎症的进展相关。
[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 卤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.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R575

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