皂角刺對肺癌的防治作用及其機(jī)制初步探討
發(fā)布時(shí)間：2018-11-23 12:24
【摘要】：肺癌是一種對生命和人類健康威脅最大的惡性腫瘤，在我國的發(fā)病率占惡性腫瘤的首位，并逐年增加，因此對肺癌的預(yù)防和治療作用的研究具有重要的意義。目前治療肺癌大多采用化學(xué)藥物，但在治療過程中存在毒副作用和多藥耐藥性等治療缺陷。中醫(yī)藥在治療腫瘤方面有毒副作用小、能提高患者的生活質(zhì)量，并且長期用藥費(fèi)用低等優(yōu)勢贏得了患者的認(rèn)可，也成為開發(fā)新型抗腫瘤藥物的重要源泉，因此篩選中醫(yī)藥抗腫瘤藥物成為藥理學(xué)領(lǐng)域研究的熱點(diǎn)。 皂角刺總黃酮是從豆科植物皂莢的干燥棘刺中提取得到的一類黃酮類化合物，各項(xiàng)探索結(jié)論已經(jīng)證明了多種腫瘤細(xì)胞增殖能夠顯著地被皂角刺總黃酮所抑制。本課題探討的目的是考察皂角刺總黃酮對肺癌細(xì)胞及肺癌模型的預(yù)防作用和治療作用，并探討其可能隱含的新機(jī)制。 本課題體外實(shí)驗(yàn)采用MTT法，檢測不同濃度的皂角刺總黃酮對小鼠肺癌細(xì)胞（Lewis）、小鼠胚肺成纖維細(xì)胞（L929）、小鼠脾淋巴細(xì)胞增值、小鼠脾淋巴細(xì)胞轉(zhuǎn)化效應(yīng)細(xì)胞及細(xì)胞黏附的影響，并用劃痕標(biāo)記染料示蹤技術(shù)觀察細(xì)胞間隙連接通訊功能；體內(nèi)實(shí)驗(yàn)采用Lewis肺癌小鼠皮下移植模型、Lewis肺癌小鼠實(shí)驗(yàn)性肺癌轉(zhuǎn)移模型和烏拉坦誘導(dǎo)的小鼠肺癌模型，評價(jià)皂角刺總黃酮對Lewis肺癌模型的預(yù)防和治療作用。通過對實(shí)驗(yàn)小鼠的外觀、體溫、生存期和自主活動觀察，評價(jià)實(shí)驗(yàn)小鼠的中醫(yī)學(xué)體征的變化；通過肺組織HE染色法，觀察肺癌組織病理學(xué)變化；通過檢測血清指標(biāo)：層粘連蛋白（LN）、血小板活化因子（PAF）、酪氨酸激酶B（TrkB）、酪氨酸激酶受體（TrkA）、小鼠免疫球蛋白G（IgG）的含量變化，評價(jià)皂角刺總黃酮對實(shí)驗(yàn)小鼠血清的影響；通過免疫組化法，觀察皂角刺總黃酮對Cx43表達(dá)的影響，驗(yàn)證其抗肺癌的機(jī)制。 體外實(shí)驗(yàn)結(jié)果顯示：皂角刺總黃酮呈劑量相關(guān)性地抑制Lewis肺癌細(xì)胞增殖（IC50=146μg/ml），但對L929胚肺成纖維細(xì)胞增殖無顯著影響。皂角刺總黃酮對細(xì)胞增殖影響較小的劑量可降低Lewis肺癌細(xì)胞粘附，并呈劑量相關(guān)性促進(jìn)Lewis肺癌細(xì)胞間連接通訊，但對L929胚肺成纖維細(xì)胞粘附無影響。同時(shí)能提高體外培養(yǎng)的小鼠脾淋巴細(xì)胞增殖率及脾淋巴細(xì)胞的殺傷力。 體內(nèi)實(shí)驗(yàn)結(jié)果顯示：與未治療的Lewis肺癌皮下移植模型和Lewis肺癌實(shí)驗(yàn)性肺癌轉(zhuǎn)移模型比較，皂角刺總黃酮高劑量和低劑量均可減緩腫瘤生長速度、阻止腫瘤轉(zhuǎn)移、延長荷瘤小鼠存活時(shí)間。未注射烏拉坦的小鼠實(shí)驗(yàn)結(jié)束時(shí)肺部均無腫瘤發(fā)生，注射烏拉坦的模型小鼠肺部有數(shù)目和大小不等的腫瘤結(jié)節(jié)，皂角刺總黃酮高劑量組和低劑量組小鼠肺部腫瘤結(jié)節(jié)明顯減少，部分小鼠未見腫瘤發(fā)生。與治療組比較模型組小鼠體溫下降、蜷縮少動；血清中LN、PAF、TrkB、TrkA水平升高，IgG含量降低。 病理及免疫組化結(jié)果顯示：與模型組的肺癌組織比較，皂角刺總黃酮高劑量組和低劑量組均能改善肺組織病理變化；而注射烏拉坦的模型小鼠肺部Cx43免疫組化顯色密度明顯降低，皂角刺總黃酮高劑量組和低劑量組均能增強(qiáng)致癌小鼠肺部的Cx43免疫組化顯色密度。 綜上所述，皂角刺總黃酮對肺癌有確切的預(yù)防和治療作用，其機(jī)制是增加免疫功能，增強(qiáng)細(xì)胞間連接通訊，恢復(fù)細(xì)胞間連接通訊的正�；瑥亩茏柚鼓[瘤生長和轉(zhuǎn)移。
[Abstract]:Lung cancer is a kind of malignant tumor which is the most serious threat to life and human health. The incidence of lung cancer is the first of the malignant tumor and is increasing year by year. Therefore, it is of great significance to study the prevention and treatment of lung cancer. The traditional Chinese medicine for treating lung cancer mainly adopts the chemical medicine, but has the defects of toxic and side effect and multi-drug resistance in the treatment process. The traditional Chinese medicine has the advantages of small toxic and side effect in the treatment of the tumor, can improve the quality of life of the patient, and has the advantages of low cost of long-term administration, and the like, and is also an important source of the development of a novel anti-tumor medicament, Therefore, the screening of anti-tumor drugs of Chinese medicine has become a hot spot in the field of pharmacology. The total flavone of the spina Gleditsiae is a kind of flavonoid compound extracted from the dried echinax of the legume of the leguminous plant, and various exploration conclusions have shown that the proliferation of various tumor cells can be significantly affected by the total flavone of the spina Gleditsiae. The purpose of this study is to study the preventive effect and therapeutic effect of the total flavone of Spina Gleditsiae on the lung cancer cell and the lung cancer model, and to explore the possible implication of the new method. Mechanism. In vitro, MTT method was used to detect the effect of different concentrations of the total flavonoids of Spina Gleditsiae on the mouse lung cancer cells (Lewis), mouse embryonic lung fibroblasts (L929), the value-added of the spleen lymphocytes of the mouse, the transformation of the spleen and lymphocytes of the mouse, and the cells. The effects of cell adhesion on adhesion were observed and the intercellular communication function was observed with a scratch-labeled dye-tracer technique. Lewis lung cancer (Lewis lung cancer) mouse subcutaneous transplantation model, Lewis lung cancer mouse experimental lung cancer metastasis model and Uratin-induced small cell lung cancer were used in vivo. Study on the model of mouse lung cancer and the prevention of Lewis lung cancer model by using the total flavonoids of Spina Gleditsiae and the pathological changes of the lung cancer tissues were observed by means of a lung tissue HE staining method; and by detecting the serum index, the layer adhesion egg Changes of the content of white (LN), platelet-activating factor (PAF), tyrosine kinase B (TrkB), tyrosine kinase receptor (TrkA), and mouse immunoglobulin G (IgG), and the effect of the total flavonoids on the serum of the experimental mice. The effect of expression to verify its resistance to The results of in vitro experiments show that the total flavonoids of the Spina Gleditsiae inhibit the proliferation of Lewis lung cancer cells in a dose-dependent manner (IC50 = 146. mu.g/ ml), but the lung of the L929 embryo is fine. There was no significant effect on the proliferation of Lewis lung cancer cells. The dose of the total flavonoids of the Spina Gleditsiae to the proliferation of the cells decreased the adhesion of the Lewis lung cancer cells and promoted the intercellular communication between the Lewis lung cancer cells in a dose-dependent manner. has no effect on the adhesion of the dimension cells, and can improve the immunity rate and the spleen of the spleen lymphocytes of the mouse cultured in vitro. The results of in vivo experiments show that the high dose and low dose of the total flavonoids in the Lewis lung cancer can slow the growth rate of the tumor and prevent the metastasis of the tumor compared with the untreated Lewis lung cancer subcutaneous transplantation model and the Lewis lung cancer experimental lung cancer metastasis model. and the survival time of the tumor-bearing mice was prolonged. Some of the mice did not meet the tumorigenesis. Compared with the treatment group, the temperature of the mice in the model group was decreased and the volume of the mice was reduced; the serum LN, PAF, TrkB, TrkA water The results of pathology and immunohistochemistry showed that the high-dose group and low-dose group could improve the pathological changes of the lung tissues compared with the lung cancer tissues of the model group. 43. The color density of the immunohistochemical staining was significantly lower, and the high-dose group and the low-dose group of the total flavonoids of the Spina Gleditsiae can enhance the lung of the cancer-induced mice. In conclusion, the total flavonoids of Spina Gleditsiae have definite prevention and treatment effect on lung cancer. The mechanism is to increase the immune function, enhance the communication between the cells, and restore the communication between the cells.
【學(xué)位授予單位】：河南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R965
本文編號：2351603
[Abstract]:Lung cancer is a kind of malignant tumor which is the most serious threat to life and human health. The incidence of lung cancer is the first of the malignant tumor and is increasing year by year. Therefore, it is of great significance to study the prevention and treatment of lung cancer. The traditional Chinese medicine for treating lung cancer mainly adopts the chemical medicine, but has the defects of toxic and side effect and multi-drug resistance in the treatment process. The traditional Chinese medicine has the advantages of small toxic and side effect in the treatment of the tumor, can improve the quality of life of the patient, and has the advantages of low cost of long-term administration, and the like, and is also an important source of the development of a novel anti-tumor medicament, Therefore, the screening of anti-tumor drugs of Chinese medicine has become a hot spot in the field of pharmacology. The total flavone of the spina Gleditsiae is a kind of flavonoid compound extracted from the dried echinax of the legume of the leguminous plant, and various exploration conclusions have shown that the proliferation of various tumor cells can be significantly affected by the total flavone of the spina Gleditsiae. The purpose of this study is to study the preventive effect and therapeutic effect of the total flavone of Spina Gleditsiae on the lung cancer cell and the lung cancer model, and to explore the possible implication of the new method. Mechanism. In vitro, MTT method was used to detect the effect of different concentrations of the total flavonoids of Spina Gleditsiae on the mouse lung cancer cells (Lewis), mouse embryonic lung fibroblasts (L929), the value-added of the spleen lymphocytes of the mouse, the transformation of the spleen and lymphocytes of the mouse, and the cells. The effects of cell adhesion on adhesion were observed and the intercellular communication function was observed with a scratch-labeled dye-tracer technique. Lewis lung cancer (Lewis lung cancer) mouse subcutaneous transplantation model, Lewis lung cancer mouse experimental lung cancer metastasis model and Uratin-induced small cell lung cancer were used in vivo. Study on the model of mouse lung cancer and the prevention of Lewis lung cancer model by using the total flavonoids of Spina Gleditsiae and the pathological changes of the lung cancer tissues were observed by means of a lung tissue HE staining method; and by detecting the serum index, the layer adhesion egg Changes of the content of white (LN), platelet-activating factor (PAF), tyrosine kinase B (TrkB), tyrosine kinase receptor (TrkA), and mouse immunoglobulin G (IgG), and the effect of the total flavonoids on the serum of the experimental mice. The effect of expression to verify its resistance to The results of in vitro experiments show that the total flavonoids of the Spina Gleditsiae inhibit the proliferation of Lewis lung cancer cells in a dose-dependent manner (IC50 = 146. mu.g/ ml), but the lung of the L929 embryo is fine. There was no significant effect on the proliferation of Lewis lung cancer cells. The dose of the total flavonoids of the Spina Gleditsiae to the proliferation of the cells decreased the adhesion of the Lewis lung cancer cells and promoted the intercellular communication between the Lewis lung cancer cells in a dose-dependent manner. has no effect on the adhesion of the dimension cells, and can improve the immunity rate and the spleen of the spleen lymphocytes of the mouse cultured in vitro. The results of in vivo experiments show that the high dose and low dose of the total flavonoids in the Lewis lung cancer can slow the growth rate of the tumor and prevent the metastasis of the tumor compared with the untreated Lewis lung cancer subcutaneous transplantation model and the Lewis lung cancer experimental lung cancer metastasis model. and the survival time of the tumor-bearing mice was prolonged. Some of the mice did not meet the tumorigenesis. Compared with the treatment group, the temperature of the mice in the model group was decreased and the volume of the mice was reduced; the serum LN, PAF, TrkB, TrkA water The results of pathology and immunohistochemistry showed that the high-dose group and low-dose group could improve the pathological changes of the lung tissues compared with the lung cancer tissues of the model group. 43. The color density of the immunohistochemical staining was significantly lower, and the high-dose group and the low-dose group of the total flavonoids of the Spina Gleditsiae can enhance the lung of the cancer-induced mice. In conclusion, the total flavonoids of Spina Gleditsiae have definite prevention and treatment effect on lung cancer. The mechanism is to increase the immune function, enhance the communication between the cells, and restore the communication between the cells.
【學(xué)位授予單位】：河南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R965
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