本文選題：肝膿腫 + 糖尿病　； 參考：《安徽醫(yī)科大學》2017年碩士論文

【摘要】：研究目的1.分析肝膿腫患者的臨床特點,觀察經(jīng)皮穿刺引流術對肝膿腫的治療效果,分析影響療效的因素。2.肺炎克雷伯菌感染后,比較糖尿病小鼠和正常小鼠肝臟炎癥反應病理學、細胞因子及炎癥信號通路蛋白表達量差異,探討糖尿病小鼠肺炎克雷伯菌肝膿腫發(fā)病率高的分子機制。研究方法1.收集上海某三甲醫(yī)院介入血管外科從2011年1月至2016年1月收治的121例肝膿腫患者臨床資料。對確診肝膿腫患者,充分抗感染的同時,CT評估病灶液化情況,在CT引導下行經(jīng)皮肝穿刺引流術,分析患者的一般資料、實驗室檢查、膿腫大小及位置、合并癥、致病菌、治療后的病死率、并發(fā)癥率、住院時間及其影響因素。2.(1)DM模型構建:有48只健康雄性的ICR小鼠,8周齡。從中隨機選取24只小鼠,用STZ腹腔注射,以120mg/kg的劑量,構建糖尿病模型,作為糖尿病組,另外24只小鼠腹腔注射等量檸檬酸鹽緩沖液,作為正常組。1周后,用血糖儀監(jiān)測血糖,如果小鼠血糖值20mmol/L,視為糖尿病模型小鼠。(2)肝膿腫模型構建:DM模型構建成功后1個月,制備3×10*7CFU/50ul肺炎克雷伯菌細菌混懸液,隨機選取糖尿病組和正常組小鼠各12只,按每只小鼠口腔灌胃3×10*8 CFU肺炎克雷伯菌的劑量感染小鼠。2組各另外8只小鼠口腔灌胃等劑量的PBS溶液。(3)實驗分組:肺炎克雷伯菌-糖尿病組、肺炎克雷伯菌-正常組、PBS-糖尿病組、PBS-正常組。(4)肝組織病理學檢查:在灌胃72h以后,在無菌條件下取出小鼠肝臟。病理學觀察比較pbs-糖尿病組、pbs-正常組、肺炎克雷伯菌-糖尿病組、肺炎克雷伯菌-正常組肝細胞水腫程度、炎癥細胞聚集情況、形成膿腫情況。(5)elisa法比較4組小鼠肝臟炎癥細胞因子il-1β、il-2、il-6、il-10、mip-1α、tnfα的表達量,westernblot觀察4組小鼠肝臟iκΚα和iκκβ、iκbα、nf-Κb及磷酸化值的表達量。研究結果1.共有121例肝膿腫患者納入研究,均做了膿液細菌培養(yǎng)或血培養(yǎng)。其中檢出肺炎克雷伯菌60例(49.59%),大腸桿菌3例(2.5%)。肝膿腫合并糖尿病60例(50.42%)。2例患者穿刺引流后死亡,病死率為1.65%,影響患者死亡率的因素為高齡、基礎疾病,膿腫直徑及實性成分;2例患者穿刺引流后出現(xiàn)肝周膿腫、腹壁膿腫,并發(fā)癥率為1.65%,對并發(fā)癥積極處理后達到臨床治愈,影響并發(fā)癥率的因素主要為手術操作欠妥;119例患者均達到臨床治愈,治愈率為98.34%,平均住院時間為(15.13±6.07)天。影響住院時間的危險因素為:膿腫個數(shù)x6(r=0.232,p=0.021),膿腫大小x7(r=0.26,p=0.005),白細胞計數(shù)x8(r=0.238,p=0.009)。進一步分析顯示影響因素與住院時間相關性的多元線性回歸方程有統(tǒng)計學意義(p0.05),多元回歸方程為:y=-3.438+3.055x6+0.527x7+0.297x8,f=5.819,r2=0.416。性別、年齡、糖尿病、致病菌、膿腫位置對住院時間的影響無統(tǒng)計學差異(p0.05)。2.stz注射一周后,用血糖儀檢測糖尿病組24只小鼠血糖值,均20mmol/l。觀察糖尿病組小鼠,毛黃、稀疏,多飲、多食、多尿,消瘦,呈現(xiàn)明顯的“三多一少”癥狀。糖尿病組小鼠血糖較正常組明顯升高(p0.05),糖尿病組與正常組小鼠體重無明顯差異(p0.05)。肺炎克雷伯菌灌胃感染小鼠后,無菌條件下取小鼠肝臟,he染色實驗結果表明:肺炎克雷伯菌-糖尿病組膿腫形成個數(shù)較肺炎克雷伯菌-正常組增多(p0.05)。elisa實驗結果表明:肺炎克雷伯菌-糖尿病組肝臟IL-1β、IL-2、IL-6、MIP-1α、TNF-α的表達量明顯高于肺炎克雷伯菌-正常組(P0.05),肺炎克雷伯菌-糖尿病組肝臟IL-1β、IL-2、IL-6、MIP-1α、TNF-α表達量高于PBS-糖尿病組(P0.05),肺炎克雷伯菌-正常組肝臟IL-1β、IL-2、IL-6、MIP-1α、TNF-α表達量高于PBS-正常組(P0.05)。Western blot實驗結果表明:肺炎克雷伯菌-糖尿病組P-IΚΚβ、P-IΚΒα、P-NFΚΒ表達量明顯高于肺炎克雷伯菌-正常組(P0.05),肺炎克雷伯菌-糖尿病組P-IΚΚα、P-IΚΚβ、P-IΚΒα、P-NFΚΒ表達量高于PBS-糖尿病組(P0.05),肺炎克雷伯菌-正常組P-IΚΚα、P-IΚΚβ、P-IΚΒα、P-NFΚΒ表達量高于PBS-正常組(P0.05)。研究結論1.CT引導下經(jīng)皮肝穿刺引流聯(lián)合抗生素能有效治療肝膿腫,具有病死率低,治愈率高,并發(fā)癥率低、住院時間短等優(yōu)點,值得臨床推廣應用。糖尿病確實是誘發(fā)肝膿腫的高危因素,但當血糖水平控制在正常范圍內時,糖尿病可以不影響住院時間。2.本實驗成功構建了ICR小鼠1型糖尿病模型及小鼠的肺炎克雷伯菌肝膿腫模型,并且證實了糖尿病小鼠肺炎克雷伯菌肝膿腫發(fā)病率增高,探索了其分子機制是細胞NF-ΚΒ信號通路的過度激活擴大了炎癥反應進程,加重了肝細胞壞死程度,導致膿腫發(fā)病率增高。
[Abstract]:Objective 1. to analyze the clinical characteristics of patients with liver abscess, observe the therapeutic effect of percutaneous drainage for liver abscess, analyze the factors that affect the curative effect of Klebsiella pneumoniae infection, compare the pathological changes of liver inflammation in diabetic mice and normal mice, the difference of the expression of cytokines and inflammatory signaling pathway protein in diabetic mice and normal mice, and explore diabetes. Molecular mechanism of high incidence of Klebsiella pneumoniae liver abscess in mice. Method 1. the clinical data of 121 patients with liver abscess treated from January 2011 to January 2016 in a three a hospital of Shanghai were collected from 121 cases of liver abscess. CT was used to evaluate the liquefaction of the lesions and the percutaneous liver puncture under the guidance of CT. Puncture drainage, analysis of the patient's general data, laboratory examination, abscess size and location, complication, pathogenic bacteria, mortality, complication rate, hospitalization time and influencing factors.2. (1) DM Model Construction: 48 healthy male ICR mice, 8 weeks of age. 24 mice were randomly selected from them, STZ intraperitoneal injection, 120mg/kg dose, configuration of 120mg/kg The diabetes model was built as a diabetic group. The other 24 mice were intraperitoneally injected with equal amount of citrate buffer. After.1 weeks in the normal group, blood glucose was monitored with blood glucose meter. If the blood glucose value of mice was 20mmol/L, the model mice were treated as diabetic model mice. (2) construction of liver abscess model: 1 months after the construction of DM model, 3 x 10*7CFU/50ul Klebsiella pneumoniae was prepared. The bacterial suspension was randomly selected and 12 mice were randomly selected from the diabetes group and the normal group. According to the dose of 3 x 10*8 CFU Klebsiella pneumoniae in each mouse oral gavage, 8 other mice were infected with PBS solution in the other 8 mice. (3) the experimental group: Klebsiella pneumoniae group, Klebsiella pneumoniae normal group, PBS- diabetic group, PBS - normal group. (4) pathological examination of liver tissue: after 72h, the mice liver was removed under aseptic condition. Pathological observation compared pbs- diabetes group, pbs- normal group, Klebsiella pneumoniae diabetes group, Klebsiella pneumoniae - normal group hepatocyte edema degree, inflammatory cell aggregation and abscess condition. (5) comparison of 4 groups by ELISA method The expression of inflammatory cytokines IL-1 beta, IL-2, IL-6, IL-10, MIP-1 alpha, TNF alpha in rat liver. Westernblot was used to observe the expression of I kappa and I kappa beta, I kappa B, I kappa B alpha, nf- I and phosphorylation in the 4 groups of mice. 1. of the study results were included in the study of 121 patients with liver abscess, and 60 cases of Klebsiella pneumoniae were detected (4 9.59%), 3 cases (2.5%) of Escherichia coli (2.5%). 60 cases of liver abscess with diabetes (50.42%).2 patients died after puncture and drainage, the fatality rate was 1.65%. The factors affecting the mortality of the patients were age, basic disease, abscess diameter and solid component; 2 patients had liver Zhou Nongzhong, abdominal abscess, complication rate 1.65% after puncture and drainage, and the complications were positive. The main factors affecting the complication rate were poor operation, 119 patients all reached clinical cure, the cure rate was 98.34%, the average hospitalization time was (15.13 + 6.07) days. The risk factors affecting the hospitalization time were X6 (r=0.232, p= 0.021), abscess size X7 (r=0.26, p=0.005), and leukocyte count X8 (r=0.238, p=). 0.009). Further analysis showed that the multivariate linear regression equation of the correlation between the influencing factors and the time of hospitalization had statistical significance (P0.05). The multiple regression equation was: y=-3.438+3.055x6+0.527x7+0.297x8, f=5.819, r2=0.416. sex, age, diabetes, pathogenic bacteria and abscess position had no statistical difference (P0.05).2.stz injection. After week, the blood glucose values of 24 mice in diabetic group were measured by blood glucose meter, and all the diabetic mice were observed by 20mmol/l.. The diabetic mice, hair yellow, sparsely, polydipsia, polyuria and emaciation showed obvious symptoms of "little more than three". The blood sugar of diabetic mice was significantly higher than that of the normal group (P0.05), and there was no significant difference between the diabetic group and the normal group (P0.05). The results of HE staining showed that the number of abscess formation in Klebsiella pneumoniae group was higher than that of Klebsiella pneumoniae normal group (P0.05).Elisa experimental results showed that the expression of IL-1 beta, IL-2, IL-6, MIP-1 A and TNF- a in Klebsiella pneumoniae diabetes group was significantly higher than that of Klebsiella pneumoniae diabetes group. The expression of IL-1 beta, IL-2, IL-6, MIP-1 alpha, TNF- alpha in Klebsiella pneumoniae normal group (P0.05) and Klebsiella pneumoniae diabetes group was higher than that of PBS- diabetic group (P0.05), and the expression of IL-1 beta, IL-2, IL-6, MIP-1 alpha in the normal group of Klebsiella pneumoniae was higher than that in the normal group. The expression of P-I in diabetic group is significantly higher than that of Klebsiella pneumoniae (P0.05), and the expression of P-I in Klebsiella pneumoniae (Klebsiella pneumoniae) is higher than that in the PBS- diabetic group (P0.05), and that of Klebsiella pneumoniae (P0.05) is higher than that in the PBS- diabetic group (P0.05). The expression of P-I is higher than that of the normal group. (P0.05). Conclusion 1.CT guided percutaneous transhepatic drainage combined with antibiotics can effectively treat liver abscess with low mortality, high cure rate, low complication rate, short hospitalization time and so on. It is worthy of clinical application. Diabetes is indeed a high risk factor for inducing liver abscess, but when blood sugar levels are controlled within the normal range, diabetes can be used. .2. model of type 1 diabetes in ICR mice and Klebsiella pneumoniae liver abscess model in mice was successfully constructed without affecting the time of hospitalization, and it was proved that the incidence of Klebsiella pneumoniae liver abscess increased in diabetic mice, and its molecular mechanism was that the excessive activation of cell NF- signaling pathway increased the process of inflammation and aggravated the process of inflammation. The degree of necrosis of liver cells leads to an increased incidence of abscesses.

【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R575.4;R587.1

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