寒、熱證候大鼠大腸癌啟動相關(guān)機(jī)制差異分析及中藥干預(yù)
發(fā)布時間：2019-03-12 11:35
【摘要】：目的:腫瘤微環(huán)境是腫瘤發(fā)生發(fā)展的一個重要影響因素,其中腫瘤相關(guān)成纖維細(xì)胞作為腫瘤微環(huán)境中最主要的組成細(xì)胞,參與腫瘤的發(fā)生發(fā)展、侵襲和轉(zhuǎn)移。本研究通過比較寒、熱兩種證型的大鼠大腸癌啟動時腫瘤相關(guān)成纖維細(xì)胞的差異,觀察大鼠大腸組織中腫瘤相關(guān)成纖維細(xì)胞的三個代表性的標(biāo)記物FAP、fsp-1和PDGFR β的表達(dá)情況,以尋求不同證候大鼠大腸腫瘤發(fā)生機(jī)制可能存在的差異。方法:將大鼠隨機(jī)分為寒證模型組、熱證模型組和空白組(雌雄各半),首先通過5周的時間,建立起寒、熱證模型及空白對照模型;然后進(jìn)行12周的大腸癌模型制作,并從寒證模型組和熱證模型組中抽取一半大鼠,分別作為寒證中藥組和熱證中藥組,額外給與反左金丸和左金丸進(jìn)行中藥反證。從第18周開始,每三周收集標(biāo)本一次,觀察大腸癌發(fā)病情況及FAP、fsp-1和PDGFRβ三個指標(biāo)在各組中的表達(dá)情況。結(jié)果:寒、熱證造模后大鼠出現(xiàn)較為明顯的寒、熱證的癥狀和體征,與寒熱證候相關(guān)的指標(biāo)ATP酶和SDH酶活性也有明顯差異;在此基礎(chǔ)上建立的大腸癌模型,通過病理檢測發(fā)現(xiàn)大鼠大腸腫瘤發(fā)生明顯,大腸癌發(fā)生早期,病理結(jié)果以寒證模型組較為嚴(yán)重,在后期時,熱證模型組癌變率更高,而且病理分期更為嚴(yán)重。而對應(yīng)的中藥干預(yù)組的腫瘤出現(xiàn)時間較晚,而且腫瘤多發(fā)生于大腸以外的器官或組織。對大腸組織進(jìn)行免疫組化和pcr檢測,結(jié)果顯示FAP、fsp-1和PDGFR β在兩個模型組的表達(dá)差異主要發(fā)生在腫瘤早期,隨著腫瘤進(jìn)展,差異逐漸不明顯;對應(yīng)的中藥干預(yù)組在腫瘤早期能夠抑制這三個標(biāo)記物的表達(dá),而隨著腫瘤進(jìn)展,抑制效果越來越弱。結(jié)論:1.在寒、熱證的基礎(chǔ)上建立大腸癌模型是可行的。該模型反映出了寒、熱的差異,誘導(dǎo)出來的大腸癌模型也具備了寒、熱證候的特點(diǎn),為進(jìn)一步研究癌變機(jī)制提供了可用的實(shí)驗(yàn)動物模型。2.寒、熱證大腸癌的差異主要體現(xiàn)在腫瘤發(fā)生早期,寒證大腸癌的發(fā)生比熱證大腸癌較晚,而病理程度更嚴(yán)重。隨著腫瘤進(jìn)展,熱證大腸癌的發(fā)病率和病理程度不亞于寒證大腸癌。3.左金丸和反左金丸對大腸癌的抑制作用主要體現(xiàn)在腫瘤早期,而且抑制效果與其藥物配比存在關(guān)系。
[Abstract]:Aim: tumor microenvironment is an important factor in the development of tumor, in which tumor-associated fibroblasts, as the most important constituent cells in tumor microenvironment, participate in the occurrence, development, invasion and metastasis of tumor. In this study, we compared the difference of tumor-associated fibroblasts during the initiation of colorectal cancer in rats with cold and heat syndromes, and observed the three representative markers of tumor-associated fibroblasts (FAP,) in the large intestine tissue of rats. The expression of fsp-1 and PDGFR 尾 was studied in order to explore the possible differences in the carcinogenesis of large intestine tumors in rats with different syndromes. Methods: rats were randomly divided into three groups: cold syndrome model group, heat syndrome model group and blank group (half female and half male). Firstly, the cold, heat syndrome model and blank control model were established after 5 weeks. Then the model of colorectal cancer was made for 12 weeks, and half of the rats were taken from the cold syndrome model group and the heat syndrome model group, respectively as the cold syndrome Chinese medicine group and the heat syndrome Chinese medicine group, and the anti-syndrome of anti-Zuo Jin Pill and Zuojin Pill were given extra. The specimens were collected every three weeks from the 18th week to observe the incidence of colorectal cancer and the expression of FAP,fsp-1 and PDGFR 尾 in each group. Results: the rats with cold and heat syndrome showed obvious cold, symptoms and signs of heat syndrome, and the activities of ATP enzyme and SDH enzyme, which were related to cold-heat syndrome, were also significantly different. The results showed that there was no significant difference between cold-heat syndrome and cold-heat syndrome. The model of colorectal cancer was established on the basis of pathological examination. It was found that the occurrence of colorectal cancer in rats was obvious in the early stage of colorectal cancer, and the pathological results were more serious in the cold syndrome model group, and in the later stage, the canceration rate in the heat syndrome model group was higher than that in the heat syndrome model group. And pathological stage is more serious. The corresponding traditional Chinese medicine intervention group appeared later, and most of the tumors occurred in organs or tissues outside of the large intestine. The results of immunohistochemistry and pcr showed that the difference of expression of FAP,fsp-1 and PDGFR 尾 between the two model groups mainly occurred in the early stage of the tumor, but the difference was not obvious with the progression of the tumor. The corresponding Chinese medicine intervention group could inhibit the expression of these three markers in the early stage of tumor, but with the progression of tumor, the inhibition effect became weaker and weaker. Conclusions: 1. It is feasible to establish colorectal cancer model on the basis of cold and heat syndrome. This model reflects the difference between cold and heat, and the induced colorectal cancer model also has the characteristics of cold and heat syndrome, which provides an available experimental animal model for further study of the mechanism of carcinogenesis. 2. The difference between cold and heat syndrome of colorectal cancer is mainly reflected in the early stage of tumorigenesis. The occurrence of cold syndrome of colorectal cancer is later than that of heat syndrome, but the degree of pathology is more serious. With the progression of tumor, the incidence and pathological degree of colorectal cancer in heat syndrome is no less than that in cold syndrome. 3. The inhibitory effects of Zuo Jin Pill and Anti-Zuo Jin Pill on colorectal cancer were mainly reflected in the early stage of tumor, and the inhibitory effect was related to the proportion of drugs.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R273
本文編號：2438739
[Abstract]:Aim: tumor microenvironment is an important factor in the development of tumor, in which tumor-associated fibroblasts, as the most important constituent cells in tumor microenvironment, participate in the occurrence, development, invasion and metastasis of tumor. In this study, we compared the difference of tumor-associated fibroblasts during the initiation of colorectal cancer in rats with cold and heat syndromes, and observed the three representative markers of tumor-associated fibroblasts (FAP,) in the large intestine tissue of rats. The expression of fsp-1 and PDGFR 尾 was studied in order to explore the possible differences in the carcinogenesis of large intestine tumors in rats with different syndromes. Methods: rats were randomly divided into three groups: cold syndrome model group, heat syndrome model group and blank group (half female and half male). Firstly, the cold, heat syndrome model and blank control model were established after 5 weeks. Then the model of colorectal cancer was made for 12 weeks, and half of the rats were taken from the cold syndrome model group and the heat syndrome model group, respectively as the cold syndrome Chinese medicine group and the heat syndrome Chinese medicine group, and the anti-syndrome of anti-Zuo Jin Pill and Zuojin Pill were given extra. The specimens were collected every three weeks from the 18th week to observe the incidence of colorectal cancer and the expression of FAP,fsp-1 and PDGFR 尾 in each group. Results: the rats with cold and heat syndrome showed obvious cold, symptoms and signs of heat syndrome, and the activities of ATP enzyme and SDH enzyme, which were related to cold-heat syndrome, were also significantly different. The results showed that there was no significant difference between cold-heat syndrome and cold-heat syndrome. The model of colorectal cancer was established on the basis of pathological examination. It was found that the occurrence of colorectal cancer in rats was obvious in the early stage of colorectal cancer, and the pathological results were more serious in the cold syndrome model group, and in the later stage, the canceration rate in the heat syndrome model group was higher than that in the heat syndrome model group. And pathological stage is more serious. The corresponding traditional Chinese medicine intervention group appeared later, and most of the tumors occurred in organs or tissues outside of the large intestine. The results of immunohistochemistry and pcr showed that the difference of expression of FAP,fsp-1 and PDGFR 尾 between the two model groups mainly occurred in the early stage of the tumor, but the difference was not obvious with the progression of the tumor. The corresponding Chinese medicine intervention group could inhibit the expression of these three markers in the early stage of tumor, but with the progression of tumor, the inhibition effect became weaker and weaker. Conclusions: 1. It is feasible to establish colorectal cancer model on the basis of cold and heat syndrome. This model reflects the difference between cold and heat, and the induced colorectal cancer model also has the characteristics of cold and heat syndrome, which provides an available experimental animal model for further study of the mechanism of carcinogenesis. 2. The difference between cold and heat syndrome of colorectal cancer is mainly reflected in the early stage of tumorigenesis. The occurrence of cold syndrome of colorectal cancer is later than that of heat syndrome, but the degree of pathology is more serious. With the progression of tumor, the incidence and pathological degree of colorectal cancer in heat syndrome is no less than that in cold syndrome. 3. The inhibitory effects of Zuo Jin Pill and Anti-Zuo Jin Pill on colorectal cancer were mainly reflected in the early stage of tumor, and the inhibitory effect was related to the proportion of drugs.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R273
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