【作者】 傅强；

【导师】 崔乃强；

【作者基本信息】 天津医科大学 ， 中西医结合临床， 2008， 博士

【摘要】 论文一严重腹腔感染所致机体免疫失衡的机理研究目的：研究严重腹腔感染所致多脏器功能障碍综合征(MODS)患者机体免疫失衡的机理及规律。对象与方法：连续观察严重腹腔感染所致MODS成年患者46例,其中男24例,女22例,年龄36～73岁,平均57.4±10.5岁,APACHE-Ⅱ评分14.5±5.62。根据患者入选第1天APACHEⅡ评分作为病情严重度分级标准将所有患者分为轻型、中型、重型、极重型4组。全部病例采用中西医结合病因及辨证治疗,观察入选后第1、3、7天APACHE-Ⅱ评分及外周血内毒素(ET)、肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、白细胞介素10(IL-10)、人类白细胞抗原DR位点(HLA-DR)、T辅助淋巴细胞1/2 (Th1/Th2)、调节性T淋巴细胞(Treg)测定,尿乳果糖／甘露醇比值(L／M)测定及所有患者SICU住院天数、总住院天数、住院费用并记录患者转归计算28天病死率等终极指标。结果：患者平均SICU住院11.06±5.40天,平均总住院18.58±5.61天,住院费用9.73±4.23万元,28天病死率为13.04%,APACHEⅡ大于15分患者病死率显著增加。APACHE-Ⅱ大于10分患者SICU住院天数、总住院天数、住院费用等预后较差。APACHE-Ⅱ小于16分的轻中型患者L/M及ET在1周内出现下降,而重症患者下降不明显。随病情严重程度加重,TNF-α及IL-6水平增加, IL-10水平在重症患者下降不明显,重症患者HLA-DR抗原表达减少,Th1/Th2比值下降,Treg水平增高。结论：严重腹腔感染时出现肠道屏障功能障碍及其引发的肠源性内毒素血症加重全身炎症反应并引发严重免疫失衡,轻型患者免疫功能在一周内有所恢复,但中型患者在一周时已出现下降趋势,重型患者免疫功能出现明显障碍,并不断加重,而极重型患者免疫功能始终处于严重抑制状态。使得感染进一步难以控制同时导致肠道以外的其他多脏器功能损害,形成并加重MODS。论文二、严重腹腔感染中医辨证规律及中西医结合疗效观察目的：研究严重腹腔感染所致MODS患者中医证型分布规律及变化特点,观察中西医结合辨证论治的疗效。对象与方法：采用八纲辨证方法连续观察外科重症监护病房46例严重腹腔感染所致MODS患者,在采取病因及对症治疗同时按不同证型进行中医辨证论治①实证治法以通里攻下为主采用复方大承气冲剂；②虚证以扶正为主,采用参芪扶正注射液；③虚实夹杂证治疗以扶正祛邪、攻补兼施为主,采用大承气冲剂同时参芪扶正注射液；④亡阴型治疗以益气敛阴、救阴生津、大补元气为主,采用参麦注射液；⑤亡阳型治疗以益气固脱、回阳救逆为主,采用参附注射液。于入选后的1、3、7天的观察记录中医证型变化并统计所有患者28天病死率。结果：所有患者第1天以里实热证和虚实夹杂证为主,第3天和第7天以虚实夹杂证为主,其次为里实热证和里虚热证,里虚寒证及亡阴／亡阳证少见,未见里实寒证,到第3天时,有39.13%实证转化为虚证,34.78%实证转化为虚实夹杂证,有15.79%虚实夹杂证转化为虚证。到第7天时,有28.57%虚证转化为虚实夹杂证。随病情加重里实热证逐渐减少,里虚热证有增加趋势。第1天表现实证的患者28天病死率较高,第7天出现虚证的患者28天病死率增高,第7天表现为虚证患者APACHE-Ⅱ评分明显增高。结论：通过中医证型来预测严重腹腔感染所致脓毒证性MODS的发展趋势及预后具有一定的临床意义。采用中药对腹部外科严重腹腔感染MODS病人进行辨证施治,在一定范围内显示出良好的临床效果。论文三、严重腹腔感染机体免疫失衡与中医辨证规律关系研究目的：研究严重腹腔感染所致MODS患者的免疫失衡特点与中医辨证分型规律的相关性,发挥中西医结合的优势指导临床治疗。对象与方法：连续观察46例严重腹腔感染所致MODS成年患者,全部病例采用中西医结合病因及辨证治疗,于入选后第1、3、7天测定外周血白细胞介素6与白细胞介素10比值(IL-6/IL-10)、人类白细胞抗原DR位点(HLA-DR)、T辅助淋巴细胞1/2(Th1/Th2)、调节性T淋巴细胞(Treg),同时观察实证、虚实夹杂证、虚证等中医证型的分布规律。结果：IL-6/IL-10比值在实证与虚实夹杂证各时间点无明显差异,虚证第7天较第1天下降,同时间比较,实证、虚实夹杂证、虚证IL-6/IL-10比值依次降低。HLA-DR水平在实证、虚实夹杂证、虚证依次降低,实证及虚实夹杂证均未发现HLA-DR<30%的病例,在虚证患者中,第7天HLA-DR全部<30%较第1天有显著差异。Th1/Th2比值在实证与虚证前3天无明显差异,第7天较第1天出现下降,虚实夹杂证一周内无变化,同时间比较,实证、虚实夹杂证、虚证Th1/Th2比值依次降低。Treg水平在实证与虚实夹杂证前3天无明显差异,虚证第3天较第1天升高,第3天与第7天无明显差异,同时间比较,实证、虚实夹杂证、虚证Treg水平依次升高。结论：在严重腹腔感染所致MODS病理过程中,反映机体促／抗炎细胞因子平衡的IL-6/IL-10比值及反映免疫功能的HLA-DR、Th1/Th2和Treg均能较为准确地反映中医虚实证型的变化,表现为实证、虚实夹杂证、虚证时,IL-6/IL-10比值、HLA-DR和Th1/Th2依次下降,而Treg水平依次升高。更多还原

【Abstract】 Paper OneThe Study on the Mechanism of Human Immune Imbalance Induced by the Severe Intra-abdominal InfectionsObjective:To explore the mechanism and rule of the immune imbalance of the patients who have multiple organ dysfunction syndrome (MODS) induced by the severe intra-abdominal infections.Object and method:46 patients with MODS, who are 24 males and 22 females with a median age of 57.4±10.5 years old(range 36～73 years), have been continuously observed. It has been fund that their average APACHE-Ⅱscore are 14.5±5.62. Based on their APACHE-Ⅱscores, the patients were divided into the light, medium, severe and extreme severe groups on the first day after they were internalized. All the cases were applied with etiological and syndrome differential treatment in the way of combining the TCM with Western medicine. On the 1st, 3rd and 7th day after they were internalized, we observe their APACHE-Ⅱscore; the examination of the endotoxin (ET), the tumor necrosis factor-α(TNF-α), the interleukin-6(IL-6), the interleukin10 (IL-10), the human leucocyte antigen DR site (HLA-DR), the helper T lymphocyte 1/2(Th1/Th2) and the regulatory T lymphocyte in the peripheral blood; the examination of the lactulose/mannitol (L/M) in the urine. Besides, we record the patients’ recovery to calculate the ultimate indexes, such as the mortality in the 28 days, the hospital days in the SICU, the total hospital days and the cost of the hospitalization.Result:The average hospital days in the SICU are 11.06±5.40, and the average total hospital days are 18.58±5.61. Addtionaly, the cost of the hospitalization is 9.73±4.23 and the mortality in the 28 days is 13.04%. But the mortality of the patients whose APACHE-Ⅱscores exceed 15 increases sharply. The prognosis, such as length of hospital stay(L.O.S.) in the SICU, the total hospital days and the cost of hospitalization and so on, of the patients whose APACHE-Ⅱscore exceeds 10 is comparatively bad. The L/M and ET of the patients whose APACHE-Ⅱscores are less than 16 in the light and medium group decreases in one week, but the patients in the severe group descend unclearly.As the pathogenic condition aggravates, the level of the TNF-αand IL-6 increases, otherwise the level of the IL-10 does not descend obviously as expected for the patients in the severe group and the HLA-DR antigen presentation decreases for the critically ill patients. The level of the Treg increases as the ratio of the Th1/Th2 descends.Conclusion:The intestinal barrier dysfunction and the intestinal endotoxemia induced by the severe intra-abdominal infections aggravate the systematic inflammatory response and lead to severe immune imbalance. It is shown in the clinical cases that the immune function of the patients in the light group recovers slightly, however, for the patients in the middle group, it has a downturn in a week, and the patients in the severe group have a significant immune dysfunction, which aggravates unceasingly. When it turns to the patients in the extreme severe group, it stays in a severe inhibitory state. All of these above make the infections hard to be controlled further and eventually cause the impairment of the multi-organ function other than the intestinal tract, which forms and aggravates MODS. Paper TwoThe Syndrome Differentiation and the Treatment Effects of TCM and Western Medicine of Severe Intra-abdominal InfectionsObjective:To conduct an exploratory study on the distribution rule of the TCM pattern of the syndrome and their changing characteristics of the patients with MODS induced by the severe intra-abdominal infections, and to observe the Efficacy of the syndrome differentiation and treatment variation in the way of combining the TCM with western medicine.Object and mothod:We apply the eight principal syndrome differentiation to observe the 46 patients with MODS induced by the severe intra-abdominal infections in the SICU, and use the syndrome differentiation and treatment variation in the TCM based on the different pattern of syndrome at the same time of the etiological and symptomatic treatment①The treatment of the sthenia syndrome is mainly achieved by TongliGongxia and uses complex DaChendQi powder preparation for infusion;②The treatment of the asthenia syndrome is achieved by enhancing immunity and adopts ShenQiFuZheng injection;③The treatment of the asthenia mixed with sthenia syndrome is achieved by enhancing immunity so as to eliminate pathogens and simultaneously apply purging-tonifying therapy and uses DaChendQi powder preparation for infusion and ShenQiFuZheng injection;④The treatment of the Yin exhaustion is achieved by retonifying Qi to retain Yin so as to produce body fluid that greatly nourish the renal Qi, and uses ShenMai injection;⑤The treatment of the Yang exhaustion is also achieved by boosting the Qi to prevent collapse and restore the Yang, and use ShenFu injection. We observe and record the changes of the TCM pattern of syndrome on the 1st,3rd,7th day after being internalized and add up the case fatality rate of all the patients in the 28 days.Result:On the 1st day, all the patients are characterized by interior-sthenia-heat syndrome and asthenia mingled with sthenia syndrome. Besides, on the 3rd and 7th days, they have major asthenia and sthenia syndrome, and then the interior-sthenia-heat syndrome and the interior-asthenia-heat syndrome. The cold syndrome with internal asthenia and the Yin exhaustion/Yang exhaustion are few and interior-sthenia-cold syndrome is rarely seen; On the 3rd day,39.13% sthenia syndromes transforms to asthenia syndromes and 34.78% sthenia syndromes transform to asthenia mingled with sthenia syndromes.15.79% asthenia mixed with sthenia syndromes transforms to asthenia syndromes. On the 7th day,28.57% asthenia syndromes transforms to asthenia mingled with sthenia syndromes. The interior-sthenia-heat syndromes decrease gradually following the aggravation of the pathogenic conditions, and the interior-asthenia-heat syndromes have a tendency of increasing. The patients with sthenia syndrome on the 1st day has a high mortality in 28 days, and the patients with asthenia syndrome on the 7th day has a high mortality in 28 days, and he patients with asthenia syndrome on the 7th day has a obviously high APACHE-Ⅱscore.Conclusion:It has some clinical significance to predict the development tendency and the prognosis of the septic MODS induced by the severe intra-abdominal infections. It draws a conclusion that Chinese herbal medicine effectively cures the patients, who has MODS induced by the severe intra-abdominal infections in abdominal surgery, based on differentiation of symptoms and signs. Paper ThreeThe Study on the Relationship between Immune Imbalance Induced by Severe Intra-abdominal Infections and Syndrome DifferentiationObjective:To explore the connections between the immune imbalance characteristics of the patients with MODS induced by the.severe intra-abdominal infections and the rule of differentiation of symptoms and signs for classification of syndrome in TCM, which integrate fully their both advantages and contribute to the instruction in clinical treatment.Object and approach:The 46 adult patients, who have MODS induced by the severe intra-abdominal infections, have been observed continuously and we apply the etiological and syndrome differentiation treatments in the way of combining the TCM and Western medicine to them. On the 1st,3rd and 7th day, we examine the ratio of the interleukin-6 and interleukin-10 (IL-6/IL-10, the human leukocyte antigen DR site(HLA-DR), the helper T lymphocyte1/2(Th1/Th2), and the regulatory T lymphocyte (Treg). In the meantime, we aslo observe the distribution rule of the TCM pattern of syndrome, such as sthenia syndrome, asthenia syndrome, asthenia syndrome mingled with sthenia syndrome and so on.Result:The. IL-6/IL-10 bears no clear difference in any time between the sthenia syndrome and asthenia syndrome and it decreases for the asthenia syndrome on the 7th day, compared with the 1st day. The comparison of the same time point indicates that the IL-6/IL-10 descends sequentially from the sthenia syndrome, asthenia syndrome mingled with sthenia syndrome to asthenia syndrome. The level of the HLA-DR descends sequentially from the sthenia syndrome, asthenia syndrome mixed with sthenia syndrome to asthenia syndrome. But there is no patients whose HLA-DR is less than 30% in the sthenia syndrome and asthenia syndrome mingled with sthenia syndrome and all the HLA-DR is less than 30% on the 7th day and has a predominant difference compared with the 1st day for the patients with asthenia syndrome. The Th1/Th2 has no specific difference in the former three days in the sthenia syndrome and asthenia syndrome, and it descends on the 7th day compared with the 1st day, and the asthenia syndrome mingled with sthenia syndrome has no change in one week. The comparison of the same time point finds that the Th1/Th2 descends sequentially from the sthenia syndrome, asthenia syndrome mingled with sthenia syndrome to asthenia syndrome. The level of the Treg has no obvious difference in the previous three days in the sthenia syndrome and asthenia syndrome mingled with sthenia syndrome and it rises up for the asthenia syndrome on the 3rd day compared with the 1st day, and there is no big difference between the 3rd day and the 7th day. The comparison of the same time points proves that the level of the Treg increases sequentially from the sthenia syndrome, asthenia syndrome mingling with sthenia syndrome to asthenia syndrome.Conclusion:In the pathological process of the MODS induced by the severe intra-abdominal infections, the IL-6/IL-10 which reflects the balance of the pro/anti-inflammatory cytokine and the HLA-DR, Thl/Th2 and Treg which shows that the immune function can all exactly reflect the change of the asthenia-sthenia pattern of syndrome of the TCM, and the IL-6/IL-10, HLA-DR and Th1/Th2 descend in order but the Treg increases in order among the sthenia syndrome, asthenia syndrome mingled with sthenia syndrome and asthenia syndrome.更多还原