【摘要】：目的：通過測定非酒精性脂肪性肝炎(NASH)肝臟組織切片中CD14、NALP3、Caspase-1的表達,探討激活NALP3炎性小體的內毒素病原相關分子模式在NASH患者肝臟炎癥發(fā)生及發(fā)展中的可能作用。 方法：收集中南大學湘雅二醫(yī)院經病理證實為非酒精性脂肪肝的住院病人的肝組織蠟塊標本26例,按脂肪性肝炎和單純性脂肪肝區(qū)分標準分為脂肪性肝炎組即NASH組(n=12)和單純性脂肪肝組即NAFL組(n=14),取經病理證實為正常的肝臟組織為正常對照組即NC組(n=10)。三組病例均從病例資料中統(tǒng)計其性別(S)、年齡(A)、體質指數(BMI)、收縮壓(SBP)、舒張壓(DBP)、甘油三酯(TG)、空腹血糖(FBG)、丙氨酸氨基轉移酶(ALT)、門冬氨酸氨基轉移酶(AST)。對三組肝組織標本的炎癥活動程度及纖維化程度進行評分。CD14、NALP3、Caspase-1測定采用免疫組織化學技術(immunohistochemistry, IHC)。應用SPSS17.0統(tǒng)計軟件進行數據處理,計數資料采用x2或fisher方法,計量資料采用獨立樣本之間T檢驗,關系判定采用pearson相關分析和logistic回歸分析,以P0.05為具有統(tǒng)計學意義、P0.01具有顯著性。 結果：臨床實驗室資料比較除年齡、性別外,體質指數(BMI)、收縮壓(SBP)、舒張壓(DBP)、甘油三酯(TG)、空腹血糖(FBG)、丙氨酸氨基轉移酶(ALT)、門冬氨酸氨基轉移酶(AST)等其余各項因素均存在統(tǒng)計學差異(P0.05)。在所選病例中以脂肪性肝炎有無(無脂肪性肝炎為0,有脂肪性肝炎為1)為因變量,各相關因素為自變量進行Logistic回歸分析,結果顯示體質指數、空腹血糖、甘油三酯、血壓是發(fā)生脂肪性肝炎的主要影響因素。 對各組CD14、NALP3、Caspase-1的含量進行半定量分析,結果表明NASH組各指標含量較NAFL組及NC組明顯增高,差異有統(tǒng)計學意義。并且各觀察指標的含量、炎癥活動程度及纖維化程度之間呈正相關。 結論：(一)肥胖、高血糖、高脂血癥、高血壓等是NASH發(fā)生的主要影響因素。 (二)內毒素作為病原相關分子模式信號通過激活NALP3炎性體,導致肝臟炎癥,可能是促進NASH發(fā)生和進展的機制之一。
[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.
【學位授予單位】：中南大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R575.1

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