本文選題：非小細胞肺癌 + 扶正解毒法　； 參考：《中國中醫(yī)科學院》2015年博士論文

【摘要】：肺癌危害大,發(fā)病率、死亡率居高不下,其中占絕大多數(shù)的是非小細胞肺癌(NSCLC).化療為目前主要的治療方式之一,但因產(chǎn)生耐藥性,療效不佳,改善化療耐藥是提高療效的有效途徑。腫瘤耐藥機制復雜,細胞凋亡受到抑制是其根本特性,癌細胞凋亡減少,細胞死亡率降低,引起化療耐藥。中醫(yī)藥結(jié)合化療可以提高療效,減輕毒副作用,為了驗證臨床效果和探索其作用機理,采用扶正解毒法(康艾注射液)配合化療,設(shè)計臨床觀察和動物實驗。目的：驗證扶正解毒中藥配合化療時增效減毒的臨床效果,以及探索其作用機理。方法：1.設(shè)計多中心前瞻隨機對照臨床試驗,入組72例非小細胞肺癌化療患者,分為單純化療組和中藥(康艾)+化療組,觀察治療前后瘤體變化和毒副反應。2.建立C57小鼠Lewis肺癌原位模型,給予扶正解毒中藥及化療干預;通過活體成像系統(tǒng)觀察小鼠瘤體變化、體重增減和記錄生存期。干預結(jié)束后取材,稱量瘤重、脾重,流式CBA方法檢測血清細胞因子,Western Blot方法檢測NF-kB p65、Bcl-2、Bcl-X1蛋白表達,Tunel方法觀察瘤細胞凋亡。結(jié)果：1.臨床研究部分,中藥(康艾)+化療組能明顯提高臨床獲益率(P0.05)；同時提高KPS評分(P0.05),在減輕化療所致的惡心、嘔吐、食欲下降等不良反應方面具有明顯的作用(P0.05),可減輕化療藥物對骨髓的抑制作用和造成的肝腎功能損傷(P0.05)。2.實驗研究部分,中藥(康艾)+化療組減少了小鼠體內(nèi)炎性細胞因子水平(P0.05),降低了NF-kB及抗凋亡蛋白Bcl-2、Bcl-X1的表達,增加了小鼠肺癌細胞的凋亡(P0.05),療程中期瘤體控制最小(P0.05),后期取材瘤重最小(P0.05),療程中體重下降最少(P0.05),生存率最高(P0.05)。結(jié)論：1.扶正解毒法配合化療,在臨床中可以起到增效減毒的作用。2.動物實驗中同樣驗證了扶正解毒法配合化療的增效減毒作用；同時推斷其可能的作用機理為,扶正解毒中藥通過降低血清炎性細胞因子水平,減少NF-kB活化,從而阻斷了“NF-kB—抗凋亡”通路,使肺癌細胞凋亡增加,提高了化療療效。
[Abstract]:Lung cancer is harmful, morbidity and mortality is high, in which the majority of non-small cell lung cancer is NSCLC. Chemotherapy is one of the main treatment methods at present, but because of drug resistance and poor curative effect, improving chemotherapeutic resistance is an effective way to improve the curative effect. The mechanism of drug resistance is complicated and the apoptosis is inhibited. The apoptosis of cancer cells decreases and the cell mortality decreases, which results in chemotherapeutic resistance. The combination of traditional Chinese medicine and chemotherapy can improve the curative effect and reduce the side effects. In order to verify the clinical effect and explore its mechanism, we designed clinical observation and animal experiment with Fuzheng detoxification method (Kangai injection) combined with chemotherapy. Objective: to verify the clinical effect of Fuzheng detoxification herbs combined with chemotherapy, and to explore its mechanism. Method 1: 1. A multicenter prospective randomized controlled clinical trial was designed. 72 patients with non-small cell lung cancer (NSCLC) were divided into simple chemotherapy group and traditional Chinese medicine (Kangai) chemotherapy group. The changes of tumor body and side effects were observed before and after treatment. The in situ model of Lewis lung cancer in C57 mice was established and treated with Fuzheng detoxification Chinese medicine and chemotherapeutic intervention. The changes of tumor body weight gain and loss and survival time were observed by in vivo imaging system. After the intervention, the tumor weight and spleen weight were measured, the serum cytokines were detected by flow cytometry, and the expression of Bcl-X1 protein in NF-kB p65 Bcl-2Bcl-X1 protein was detected by NF-kB p65 Bcl-2Bcl-X1. Apoptosis of tumor cells was observed by Tunel method. The result is 1: 1. In the clinical study, the Chinese medicine (Kangai) chemotherapy group could significantly increase the clinical benefit rate (P 0.05), and increase the KPS score (P 0.05) in reducing the nausea and vomiting caused by chemotherapy. The adverse reactions such as loss of appetite have obvious effect on P0.05, which can reduce the inhibitory effect of chemotherapeutic drugs on bone marrow and the damage of liver and kidney function caused by P0.05. 2. In the experimental study, the Chinese medicine (Kangai) chemotherapy group decreased the level of inflammatory cytokines (P0.05), and the expression of NF-kB and anti-apoptotic protein Bcl-X1 in mice. The apoptosis of lung cancer cells in mice was increased (P 0.05), the tumor body control was the lowest (P 0.05), the tumor weight was the lowest (P 0.05), the weight loss was the least (P 0.05), and the survival rate was the highest (P 0.05) during the course of treatment. Conclusion 1. Fuzheng detoxification method combined with chemotherapy, in clinical can play a synergistic and detoxification role. 2. In animal experiments, the synergistic and detoxifying effect of Fuzheng detoxification method combined with chemotherapy was also verified, and its possible mechanism was inferred that Fuzheng detoxification herbs could reduce the activation of NF-kB by reducing the level of serum inflammatory cytokines. Thus, the NF-kB-anti-apoptosis pathway was blocked, which increased the apoptosis of lung cancer cells and improved the chemotherapeutic effect.
【學位授予單位】：中國中醫(yī)科學院
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R734.2

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