本文選題：行健湯 + 胃癌��； 參考：《南京中醫(yī)藥大學(xué)》2017年博士論文

【摘要】：研究目的:以孟河醫(yī)派學(xué)術(shù)思想為指導(dǎo),結(jié)合導(dǎo)師臨床經(jīng)驗(yàn),通過臨床對照研究,觀察加減行健湯聯(lián)合化療,對比單純化療組,治療胃癌術(shù)后脾胃氣虛證患者的臨床療效及對生活質(zhì)量的影響。研究其成分薯蕷皂苷抑制腫瘤細(xì)胞增殖的機(jī)制。研究方法:本研究分臨床觀察和實(shí)驗(yàn)研究兩部分。臨床觀察部分:選擇60例胃癌術(shù)后脾胃氣虛證患者,隨機(jī)分為對照組-單純化療組及治療組-中藥聯(lián)合化療組,觀察周期3個月,觀察兩組治療前后的中醫(yī)癥狀、生活質(zhì)量、腫瘤指標(biāo)、淋巴細(xì)胞亞群變化,以及化療后毒副反應(yīng),并統(tǒng)計(jì)分析結(jié)果。實(shí)驗(yàn)研究部分:首先,運(yùn)用實(shí)時定量熒光PCR法檢測胃癌組織中長鏈非編碼RNAH19、HOTAIR、MALAT1的表達(dá),選擇表達(dá)量最高的HOTAIR,對比臨床資料,說明HOTAIR的表達(dá)與臨床病理因素之間的相關(guān)性。其次,用實(shí)時定量熒光PCR法檢測胃癌細(xì)胞SGC-7901、HGC-27、MGC-803細(xì)胞株及正常黏膜上皮GES-1細(xì)胞株中三種長鏈非編碼RNA的表達(dá)情況。選擇MGC-803細(xì)胞及1ncRNAHOTAIR行下一步實(shí)驗(yàn)。用si-RNA下調(diào)HOTAIR的表達(dá)后,MTT法檢測胃癌MGC-803細(xì)胞增殖情況,說明HOTAIR對于胃癌細(xì)胞的作用。第三步,研究薯蕷皂苷抗胃癌增殖機(jī)制。運(yùn)用MTT法檢測薯蕷皂苷對于胃癌MGC-803細(xì)胞的抑制作用。用si-HOTAIR、薯蕷皂苷同時干預(yù)胃癌MGC-803細(xì)胞,對比陰性對照組,用實(shí)時定量PCR法檢測胃癌細(xì)胞中的HOTAIR相對表達(dá)量,MTT法、細(xì)胞克隆形成實(shí)驗(yàn)觀察胃癌細(xì)胞增殖情況,研究薯蕷皂苷的抗胃癌增殖機(jī)制。研究結(jié)果:臨床觀察部分:有效評價患者共57例,治療組29例,對照組28例。經(jīng)過治療,治療組在中醫(yī)癥狀改善方面優(yōu)于對照組,尤其是在食少納呆、體倦乏力、食后腹脹、大便異常、神疲懶言、面色萎黃、排便無力方面,經(jīng)過治療,治療組優(yōu)于對照組,兩組治療后比較有統(tǒng)計(jì)學(xué)差異(P0.05)。生活質(zhì)量評價方面,EORTC QLQ-ST052量表評分方面,治療組治療后在軀體功能、角色功能、情緒功能、總健康、疲倦、失眠、食欲喪失、便秘、腹瀉、吞咽困難、返流、進(jìn)食受限等方面較對照組治療后改善,兩組治療后比較有統(tǒng)計(jì)學(xué)差異(P0.05)。FACT-G評分量表,治療組經(jīng)過治療,在生理狀況及功能狀況改善方面優(yōu)于對照組,有統(tǒng)計(jì)學(xué)差異(P0.05)。經(jīng)過治療,治療組在淋巴細(xì)胞亞群改善方面優(yōu)于對照組,兩組治療后比較有統(tǒng)計(jì)學(xué)差異(P0.05)。兩組在腫瘤指標(biāo)變化方面無統(tǒng)計(jì)學(xué)差異(P0.05)。PFS方面,隨訪日期為2016年10月30日,中藥聯(lián)合化療組中位進(jìn)展時間8.0±0.21個月,化療組中位進(jìn)展時間為7.0±0.65個月,兩組PFS時間無統(tǒng)計(jì)學(xué)差異(P0.05)。毒副反應(yīng)方面,治療前后兩組在骨髓抑制、胃腸道反應(yīng)、肝功能異常、神經(jīng)毒性、皮膚反應(yīng)方面無統(tǒng)計(jì)學(xué)差異(P0.05)。實(shí)驗(yàn)部分:在胃癌組織中長鏈非編碼RNAHOTAIR、H19、MALAT-1均高表達(dá)。其中,HOTAIR表達(dá)與胃癌的分期、淋巴結(jié)轉(zhuǎn)移、浸潤深度相關(guān)。胃癌MGC-803、SGC-7901、HGC-27細(xì)胞株中,HOTAIR、MALAT-1也高表達(dá)。選擇胃癌MGC-803細(xì)胞和HOTAIR進(jìn)行后續(xù)實(shí)驗(yàn)。用si-RNA下調(diào)胃癌MGC-803細(xì)胞中的HOTAIR表達(dá)后,胃癌細(xì)胞增殖受到抑制�？梢哉J(rèn)為HOTAIR高表達(dá)可促進(jìn)胃癌MGC-803細(xì)胞增殖。薯蕷皂苷為加減行健湯的抗腫瘤成分之一。用薯蕷皂苷干擾胃癌MGC-803細(xì)胞后,胃癌MGC-803細(xì)胞中的HOTAIR表達(dá)量下降,胃癌細(xì)胞增殖也受到抑制。認(rèn)為通過下調(diào)胃癌細(xì)胞中HOTAIR的表達(dá)從而抑制胃癌細(xì)胞增殖是薯蕷皂苷抗腫瘤的可能機(jī)制。結(jié)論:加減行健湯配合化療能起到提高生活質(zhì)量,改善癥狀,提高機(jī)體免疫功能的作用。實(shí)驗(yàn)研究證實(shí),其抗腫瘤成分薯蕷皂苷可能通過下調(diào)胃癌細(xì)胞中HOTAIR的表達(dá)從而抑制胃癌細(xì)胞增殖。
[Abstract]:Objective: To observe the clinical curative effect and the effect on the quality of life of the patients with spleen and stomach qi deficiency after the operation of gastric cancer and study the mechanism of diosgenin to inhibit the proliferation of tumor cells by combining the clinical experience of the Mencius medical school and combining the clinical experience of the tutor to observe the combined chemotherapy and subtraction of the combination chemotherapy and subtraction of the combination chemotherapy and the simple chemotherapy group. Research methods: This study was divided into two parts of clinical observation and experimental study. Clinical observation part: select 60 cases of spleen and stomach qi deficiency after gastric cancer surgery, randomly divided into control group - simple chemotherapy group and treatment group - Chinese medicine combined chemotherapy group, observe the period of 3 months, observe the symptoms of traditional Chinese medicine, quality of life, tumor index, lymphocyte subgroup before and after treatment of two groups. Group changes, toxicity and side effects after chemotherapy, and statistical analysis results. Experimental research part: first, real-time quantitative fluorescence PCR method was used to detect the expression of long chain noncoding RNAH19, HOTAIR, MALAT1 in gastric cancer tissue, and the highest expression of HOTAIR was selected. The correlation between the expression of HOTAIR and the clinicopathological factors was compared. Secondly, the correlation between the expression of HOTAIR and the clinicopathological factors was compared. The expression of three long chain non coded RNA in gastric cancer cells SGC-7901, HGC-27, MGC-803 cell lines and normal mucosal epithelial GES-1 cell lines was detected by real-time quantitative fluorescence PCR. The next experiment of MGC-803 cells and 1ncRNAHOTAIR was selected. The proliferation of gastric cancer MGC-803 cells was detected by si-RNA downregulation and MTT method was used to detect the proliferation of gastric cancer MGC-803 cells. The third step was to study the anti gastric cancer proliferation mechanism of diosgenin. The inhibitory effect of diosgenin on gastric cancer MGC-803 cells was detected by MTT. Si-HOTAIR and Diosgenin were used to interfere with the MGC-803 cells of gastric cancer at the same time, and the negative control group was compared with the negative control group. The relative expression of HOTAIR in gastric cancer cells was detected by real-time quantitative PCR, MTT Method, cell clone formation test to observe the proliferation of gastric cancer cells and study the anti gastric cancer proliferation mechanism of diosgenin. The results of the study: clinical observation part: the effective evaluation of 57 patients, 29 cases in the treatment group and 28 cases in the control group. After treatment, the treatment group is better than the control group in the improvement of Chinese medicine symptoms, especially in the diet, body fatigue and fatigue. After the abdominal distention, abnormality of stool, deity laziness, pale yellow and defecation, the treatment group was better than the control group. The two groups were compared with the control group (P0.05). The quality of life evaluation, the EORTC QLQ-ST052 scale score, the treatment group after treatment in the body function, function, emotional function, total health, fatigue, insomnia, food Loss of desire, constipation, diarrhea, dysphagia, reflux, food restriction, and other aspects of improvement after treatment compared with the control group, the two groups after treatment had a statistically significant difference (P0.05).FACT-G score scale, the treatment group after treatment, the physiological status and functional status improvement is better than the control group, there is a statistical difference (P0.05). After treatment, the treatment group in lymphatic thin. The improvement of cell subgroup was better than that of the control group. The two groups had statistical difference after treatment (P0.05). There was no statistical difference between the two groups (P0.05).PFS, the date of follow-up was October 30, 2016, the median progress time of the combination chemotherapy group was 8 + 0.21 months, the median progression time of the chemotherapy group was 7 + 0.65 months, and the two groups of PFS There was no statistical difference (P0.05). In the side effects, there was no statistical difference between the two groups in bone marrow suppression, gastrointestinal reaction, liver dysfunction, neurotoxicity, and skin reaction (P0.05). Experimental part: the high expression of long chain non coded RNAHOTAIR, H19, MALAT-1 in gastric cancer tissues. Among them, HOTAIR expression and gastric carcinoma staging, lymph nodes Metastasis, infiltration depth related. Gastric cancer MGC-803, SGC-7901, HGC-27 cell lines, HOTAIR, MALAT-1 also high expression. Select gastric cancer MGC-803 cells and HOTAIR for follow-up experiments. The proliferation of gastric cancer cells was inhibited after si-RNA down-regulation of HOTAIR expression in gastric cancer MGC-803 cells. It can be considered that HOTAIR high expression can promote the proliferation of gastric cancer MGC-803 cells. Diosgenin is one of the antineoplastic ingredients in the addition of diosgenin. After diosgenin interferes with gastric cancer MGC-803 cells, the expression of HOTAIR in gastric cancer MGC-803 cells is decreased and the proliferation of gastric cancer cells is inhibited. It is considered that the possible mechanism of diosgenin anti tumor by reducing the expression of HOTAIR in gastric cancer cells and inhibiting the proliferation of gastric cancer cells is the possible mechanism of diosgenin antitumor. Conclusion: the addition and subtraction of Jian Jian decoction combined with chemotherapy can improve the quality of life, improve the symptoms and improve the immune function of the body. The experimental study has proved that the antitumor component of diosgenin may inhibit the proliferation of gastric cancer cells by down regulating the expression of HOTAIR in gastric cancer cells.
【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R735.2

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