【摘要】：目的：基于前期研究基礎(chǔ),探討乙肝病毒相關(guān)慢加急性肝衰竭(Hepatitis B Virus associated acute on chronic liver failure, HBV-ACLF)外周血T淋巴細(xì)胞頻數(shù)與預(yù)后的相關(guān)性；基于HBV-ACLF正虛病機(jī)的益氣健脾法治療改善其預(yù)后的免疫學(xué)機(jī)制。方法：選擇南京市第二醫(yī)院肝病科收住入院的基礎(chǔ)病變?yōu)槁砸倚筒《拘愿窝谆蚋斡不穆蛹毙愿嗡ソ?診斷符合2012年修訂的《肝衰竭防治指南》的標(biāo)準(zhǔn))患者共97例；隨機(jī)分為治療組31例,對(duì)照組66例。對(duì)照組采用西醫(yī)綜合內(nèi)科治療；治療組采用益氣健脾法聯(lián)合西醫(yī)綜合內(nèi)科治療,療程4周。觀察兩組患者治療前與治療后中醫(yī)癥候積分、血常規(guī)、肝功能、凝血功能、MELD評(píng)分以及CD3+、CD4+、CD8+(CTL)T淋巴細(xì)胞及CD4+CD25+Treg細(xì)胞頻數(shù)等免疫學(xué)指標(biāo),同時(shí),選取23例正常人和23例慢乙肝患者以便于與HBV-ACLF患者對(duì)照。結(jié)果：1)與正常人和慢乙肝患者比較,HBV-ACLF外周血白細(xì)胞總數(shù)明顯上升,淋巴細(xì)胞比例、CD3+T淋巴細(xì)胞頻數(shù)明顯降低。2)外周血白細(xì)胞總數(shù)、淋巴細(xì)胞比例、CD3+T淋巴細(xì)胞頻數(shù)、CD4+CD25+Treg細(xì)胞頻數(shù)的變化與反映HBV-ACLF病情程度及進(jìn)展的實(shí)驗(yàn)室指標(biāo)TBil、PTA和MELD評(píng)分具有相關(guān)性。3)與對(duì)照組比較,基于正虛病機(jī)的中醫(yī)藥益氣健脾法治療的治療組,其療效明顯優(yōu)于對(duì)照組,癥狀積分明顯下降、實(shí)驗(yàn)室指標(biāo)TBil、ALT和MELD評(píng)分明顯改善,淋巴細(xì)胞比例、T淋巴細(xì)胞頻數(shù)明顯升高,并且變化的幅度也明顯大于對(duì)照組。結(jié)論：1)HBV-ACLF一旦發(fā)生,白細(xì)胞、淋巴細(xì)胞和T淋巴細(xì)胞顯示出與正常人和慢性乙型肝炎不同的特點(diǎn)：外周血白細(xì)胞總數(shù)明顯上升；外周血淋巴細(xì)胞和T淋巴細(xì)胞比例明顯降低。體現(xiàn)了HBV-ACLF一旦發(fā)生,機(jī)體的免疫處于某種“耗損”狀態(tài),與中醫(yī)“正虛”病機(jī)有一定程度的“吻合”。2)HBV-ACLF患者外周血白細(xì)胞、淋巴細(xì)胞和T淋巴細(xì)胞特點(diǎn)與病情嚴(yán)重程度相關(guān):外周血白細(xì)胞總數(shù)的上升及淋巴細(xì)胞和T淋巴細(xì)胞頻數(shù)的降低愈明顯,提示病情愈嚴(yán)重。3)HBV-ACLF患者外周血白細(xì)胞、淋巴細(xì)胞和T淋巴細(xì)胞的變化與預(yù)后相關(guān)：白細(xì)胞總數(shù)的上升趨勢(shì)和淋巴細(xì)胞、T淋巴細(xì)胞頻數(shù)的下降趨勢(shì)越緩,則患者病情進(jìn)展越慢,預(yù)后越好；反之病情進(jìn)展越快,病情越重,預(yù)后亦越差。4)基于正虛病機(jī)的中醫(yī)藥益氣健脾法治療HBV-ACLF改善T淋巴細(xì)胞的“耗損”狀態(tài),從而改善預(yù)后：益氣健脾法治療后中醫(yī)癥候評(píng)分,肝功能、MELD評(píng)分均明顯改善,從而改善了預(yù)后。調(diào)節(jié)外周血淋巴細(xì)胞、T淋巴細(xì)胞頻數(shù)的“耗損”狀態(tài),改善免疫功能是其改善預(yù)后的部分免疫學(xué)機(jī)制。
[Abstract]:Objective: to investigate the correlation between the frequency of peripheral blood T lymphocytes and prognosis in patients with hepatitis B virus associated chronic and acute hepatic failure (Hepatitis B Virus associated acute on chronic liver failure, HBV-ACLF) based on the previous study. The immunological mechanism of invigorating qi and invigorating spleen based on the pathogenesis of HBV-ACLF deficiency to improve the prognosis. Methods: 97 patients with chronic hepatitis B or liver cirrhosis with chronic and acute liver failure were selected from the Department of Hepatology, second Hospital of Nanjing City, in accordance with the criteria of 2012 revised guidelines for Prevention and treatment of liver failure, and 97 patients were diagnosed as chronic hepatitis B or liver cirrhosis. They were randomly divided into treatment group (n = 31) and control group (n = 66). The control group was treated with western medicine and the treatment group was treated by tonifying qi and invigorating spleen combined with western medicine for 4 weeks. The scores of TCM symptoms, blood routine, liver function, coagulation function, MELD score and the frequency of CD3, CD4, CD8 (CTL) T lymphocytes and CD4 CD25 Treg cells were observed before and after treatment in the two groups. Twenty-three normal subjects and 23 chronic hepatitis B patients were selected for comparison with HBV-ACLF patients. Results: 1) compared with normal persons and patients with chronic hepatitis B, the total number of peripheral blood leukocytes in HBV-ACLF increased significantly, the proportion of lymphocytes and the frequency of CD3 T lymphocytes decreased significantly. 2) the total number of white blood cells in peripheral blood and the proportion of lymphocytes in peripheral blood were significantly decreased. The changes of CD3 T lymphocyte frequency and CD4 CD25 Treg cell frequency were correlated with the scores of TBil,PTA and MELD, which could reflect the severity and progression of HBV-ACLF. 3) compared with the control group, there was no significant difference between the control group and the control group (P < 0.05). Based on the pathogenesis of positive deficiency, the curative effect of TCM Yiqi Jianpi treatment group was obviously better than that of the control group, the symptom integral was obviously decreased, the TBil,ALT and MELD scores of laboratory indexes were improved obviously, and the proportion of lymphocyte was also improved. The frequency of T lymphocyte increased significantly, and the range of change was significantly larger than that of the control group. Conclusion: 1) once HBV-ACLF occurs, leukocytes, lymphocytes and T lymphocytes show different characteristics from those of normal persons and chronic hepatitis B. the total number of leukocytes in peripheral blood is obviously increased. The ratio of peripheral blood lymphocytes to T lymphocytes decreased significantly. It shows that once HBV-ACLF occurs, the immunity of the body is in a state of "depletion", which is consistent with the pathogenesis of "positive deficiency" in traditional Chinese medicine to a certain extent. 2) White blood cells in peripheral blood of patients with HBV-ACLF. The characteristics of lymphocytes and T lymphocytes were correlated with the severity of the disease: the higher the total number of white blood cells and the lower the frequency of lymphocytes and T lymphocytes in peripheral blood, the more serious the condition was. 3) the more serious the HBV-ACLF patients were, the more serious the disease was. The change of lymphocyte and T lymphocyte is related to prognosis: the increasing trend of white blood cell count and lymphocyte, the slower the decreasing trend of T lymphocyte frequency, the slower the patient's condition progress and the better the prognosis; On the contrary, the faster the disease progresses, the more serious the condition and the worse the prognosis. 4) the therapy of tonifying qi and invigorating the spleen, which is based on the mechanism of positive deficiency, is used to treat HBV-ACLF to improve the "depletion" of T lymphocytes. In order to improve the prognosis: after therapy of invigorating qi and invigorating the spleen, the scores of TCM symptoms, liver function and MELD were obviously improved, thus the prognosis was improved. Regulating the "depletion" state of peripheral blood lymphocytes and T lymphocyte frequency and improving immune function are some of the immunological mechanisms for improving the prognosis of peripheral blood lymphocytes and T lymphocytes.
【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R259

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