【摘要】：目的：觀察六神丸聯(lián)合放療治療食管癌的近期療效、不良反應(yīng)、生活質(zhì)量改善情況及對(duì)食管癌炎性微環(huán)境與血管生成的作用及其相關(guān)機(jī)制。 方法：(1)臨床觀察：將30例食管癌患者分為實(shí)驗(yàn)組和對(duì)照組,對(duì)照組采用單純放射治療,實(shí)驗(yàn)組采用六神丸配合放療進(jìn)行治療。一個(gè)療程后,評(píng)價(jià)兩組近期療效、生活質(zhì)量改善情況、不良反應(yīng)。 (2)實(shí)驗(yàn)研究：采用皮下注射食管癌細(xì)胞懸液建立食管癌移植瘤裸鼠模型,并予以六神丸干預(yù)食管癌移植瘤裸鼠模型,動(dòng)態(tài)觀察各組裸鼠生存情況、瘤體生長情況、病理組織學(xué)觀察,繪制瘤體生長曲線,計(jì)算抑瘤率,采用RT-PCR法和Western-blot測定瘤組織腫瘤壞死因子一α(TNF-α)、白介素-6(IL-6)、核轉(zhuǎn)錄因子一KB(NF-κKB)、血管內(nèi)皮生長因子(VEGF)水平,免疫組織化學(xué)方法測定腫瘤微血管密度(MVD)。 結(jié)果：(1)臨床觀察：兩組患者在近期療效比較上無顯著差異,但是實(shí)驗(yàn)組較對(duì)照組生活質(zhì)量改善情況明顯,且在不良反應(yīng)的發(fā)生率上明顯低于對(duì)照組。 (2)實(shí)驗(yàn)研究：六神丸能在一定程度上抑制食管癌移植瘤的生長,六神丸高、中、低劑量組抑瘤率與模型組比較,明顯高于模型組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；各六神丸組食管癌移植瘤組織內(nèi)TNF-α、IL-6、NF-κB表達(dá)活性較模型組明顯下調(diào)。各六神丸組食管癌移植瘤組織內(nèi)VEGF、MVD表達(dá)活性明顯低于模型組。 結(jié)論：(1)臨床研究：六神丸聯(lián)合放療方案雖不能提高食管癌患者近期療效,但與單純放療比較,能顯著改善患者生活質(zhì)量,降低不良反應(yīng)的發(fā)生。 (2)實(shí)驗(yàn)研究：1)六神丸能抑制食管癌移植瘤的生長；2)六神丸通過下調(diào)食管癌炎性微環(huán)境中TNF-α、IL-6、NF-κB的表達(dá),調(diào)節(jié)TNF-α--NF-KB通路,可能是其抗腫瘤機(jī)制之一。3)六神丸能通過調(diào)節(jié)瘤組織內(nèi)VEGF、MVD的表達(dá)活性,抑制血管生成是其抗腫瘤機(jī)制之一。4)六神丸通過調(diào)節(jié)腫瘤炎性微環(huán)境中TNF-α--NF-κKB通路,調(diào)控VEGF表達(dá),抑制腫瘤血管生成,可能是其抗腫瘤機(jī)制之一。
[Abstract]:Aim: to observe the short-term efficacy, adverse reactions, improvement of quality of life (QOL) and the effect on inflammatory microenvironment and angiogenesis of esophageal carcinoma treated with Liushen pill combined with radiotherapy. Methods: (1) Clinical observation: 30 patients with esophageal cancer were divided into experimental group and control group. The control group was treated with radiotherapy alone, and the experimental group was treated with Liushen pill combined with radiotherapy. After a course of treatment, we evaluated the short-term efficacy, improvement of quality of life and adverse reactions between the two groups. (2) Experimental study: the nude mice model of transplanted esophageal carcinoma was established by subcutaneous injection of esophageal cancer cell suspension, and the nude mice model of transplanted esophageal carcinoma was treated with Liushen Pill, and the survival and the growth of tumor were observed dynamically in each group of nude mice. The tumor growth curve was drawn and the tumor inhibition rate was calculated. The tumor necrosis factor-偽 (TNF- 偽), interleukin-6 (IL-6) and nuclear factor-KB (NF- 魏 KB) in tumor tissue were measured by RT- PCR and Western-blot. The level of vascular endothelial growth factor (VEGF) and the detection of tumor microvessel density (MVD).) by immunohistochemical method Results: (1) Clinical observation: there was no significant difference in the short-term curative effect between the two groups, but the quality of life in the experimental group was better than that in the control group, and the incidence of adverse reactions in the experimental group was significantly lower than that in the control group. (2) Experimental study: Liushen pill can inhibit the growth of transplanted tumor of esophageal cancer to a certain extent, high, middle and low dose of Liushen pill compared with the model group, the inhibition rate is significantly higher than the model group, the difference is statistically significant (P0.05); Compared with the model group, the expression of TNF- 偽 and IL-6,NF- 魏 B in the transplanted tumor tissue of esophageal carcinoma were significantly down-regulated in each six-shenwan group. The expression of VEGF,MVD in the transplanted tumor tissue of esophageal carcinoma was significantly lower than that in the model group. Conclusion: (1) Clinical study: although Liushen pill combined with radiotherapy can not improve the short-term efficacy of esophageal cancer patients, compared with radiotherapy alone, it can significantly improve the quality of life and reduce the occurrence of adverse reactions. (2) Experimental study: 1) Liushen pill can inhibit the growth of transplanted tumor of esophageal cancer; 2) Liushen Pill can regulate the expression of TNF- 偽 and IL-6,NF- kappa B in inflammatory microenvironment of esophageal cancer and regulate the TNF- 偽-NF-KB pathway, which may be one of its anti-tumor mechanisms. 3) Liushen Pill can regulate VEGF, in tumor tissue by regulating the expression of TNF 偽 and VEGF, kappa B in the inflammatory microenvironment of esophageal cancer. The expression of MVD and the inhibition of angiogenesis are one of its anti-tumor mechanisms. 4) Liushen Pill regulates the expression of VEGF and inhibits tumor angiogenesis by regulating the TNF- 偽-NF- kappa KB pathway in inflammatory microenvironment of tumor. It may be one of its anti-tumor mechanisms.
【學(xué)位授予單位】：湖南中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R735.1

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