CD14、NALP3、Caspase-1在非酒精性脂肪性肝炎患者肝组织中的表达和意义

发布时间：2018-09-19 09:54

【摘要】：目的：通过测定非酒精性脂肪性肝炎(NASH)肝脏组织切片中CD14、NALP3、Caspase-1的表达,探讨激活NALP3炎性小体的内毒素病原相关分子模式在NASH患者肝脏炎症发生及发展中的可能作用。方法：收集中南大学湘雅二医院经病理证实为非酒精性脂肪肝的住院病人的肝组织蜡块标本26例,按脂肪性肝炎和单纯性脂肪肝区分标准分为脂肪性肝炎组即NASH组(n=12)和单纯性脂肪肝组即NAFL组(n=14),取经病理证实为正常的肝脏组织为正常对照组即NC组(n=10)。三组病例均从病例资料中统计其性别(S)、年龄(A)、体质指数(BMI)、收缩压(SBP)、舒张压(DBP)、甘油三酯(TG)、空腹血糖(FBG)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)。对三组肝组织标本的炎症活动程度及纤维化程度进行评分。CD14、NALP3、Caspase-1测定采用免疫组织化学技术(immunohistochemistry, IHC)。应用SPSS17.0统计软件进行数据处理,计数资料采用x2或fisher方法,计量资料采用独立样本之间T检验,关系判定采用pearson相关分析和logistic回归分析,以P0.05为具有统计学意义、P0.01具有显著性。结果：临床实验室资料比较除年龄、性别外,体质指数(BMI)、收缩压(SBP)、舒张压(DBP)、甘油三酯(TG)、空腹血糖(FBG)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)等其余各项因素均存在统计学差异(P0.05)。在所选病例中以脂肪性肝炎有无(无脂肪性肝炎为0,有脂肪性肝炎为1)为因变量,各相关因素为自变量进行Logistic回归分析,结果显示体质指数、空腹血糖、甘油三酯、血压是发生脂肪性肝炎的主要影响因素。对各组CD14、NALP3、Caspase-1的含量进行半定量分析,结果表明NASH组各指标含量较NAFL组及NC组明显增高,差异有统计学意义。并且各观察指标的含量、炎症活动程度及纤维化程度之间呈正相关。结论：(一)肥胖、高血糖、高脂血症、高血压等是NASH发生的主要影响因素。 (二)内毒素作为病原相关分子模式信号通过激活NALP3炎性体,导致肝脏炎症,可能是促进NASH发生和进展的机制之一。
[Abstract]:Aim: to investigate the possible role of endotoxin-associated molecular model of activating NALP3 inflammatory corpuscles in the occurrence and development of liver inflammation in patients with NASH by detecting the expression of CD14,NALP3,Caspase-1 in liver sections of (NASH) patients with non-alcoholic steatohepatitis. Methods: a total of 26 samples of paraffin tissue from patients with non-alcoholic fatty liver confirmed by pathology in Xiangya second Hospital of Central South University were collected. According to the criteria of differentiating fatty hepatitis from simple fatty liver, they were divided into two groups: NASH group (n = 12) and simple fatty liver group (n ~ (14). The normal liver tissue proved to be normal by pathology was normal control group (n ~ (10). Three groups of patients were counted from the data of their sex (S), age (A), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST). The degree of inflammatory activity and fibrosis in three groups of liver tissue specimens were evaluated. CD14 NALP3Caspase-1 was determined by immunohistochemical technique (immunohistochemistry, IHC). The data were processed by SPSS17.0 statistical software. The counting data were analyzed by X2 or fisher method, the measurement data were measured by T test among independent samples, and the relationship was determined by pearson correlation analysis and logistic regression analysis. Results: in addition to age and sex, the clinical laboratory data were compared. Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and other factors were statistically different (P0.05). In the selected cases, whether there was fatty hepatitis (0 for non-fat hepatitis and 1 for fatty hepatitis) was used as dependent variable, and the correlation factors were independent variables for Logistic regression analysis. The results showed that body mass index, fasting blood glucose, triglyceride were the main factors. Blood pressure is the main influencing factor of fatty hepatitis. The results showed that the content of CD14,NALP3,Caspase-1 in NASH group was significantly higher than that in NAFL group and NC group, and the difference was statistically significant. There was a positive correlation between the content of the observed indexes, the degree of inflammatory activity and the degree of fibrosis. Conclusion: (1) Obesity, hyperglycemia, hyperlipidemia and hypertension are the main influencing factors of NASH. (2) Endotoxin, as a signal of pathogen-associated molecular model, may be one of the mechanisms of promoting the pathogenesis and progression of NALP3 by activating the inflammatory body of NASH and leading to hepatic inflammation.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R575.1

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