本文選題：丙氨瑞林 + 子宮內(nèi)膜癌��； 參考：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：研究目的 促性腺激素釋放激素類似物已應(yīng)用于臨床治療多種腫瘤,但其具體作用機(jī)制仍有待于研究。本課題通過(guò)觀察不同劑量的丙氨瑞林(Alarelin)對(duì)子宮內(nèi)膜癌裸鼠移植瘤的生長(zhǎng)抑制和PinX1表達(dá)的影響以及兩者之間的相互關(guān)系,探討促性腺激素釋放激素類似物影響端粒酶促腫瘤通路抑制腫瘤生長(zhǎng)可能的作用機(jī)制。 研究方法 人子宮內(nèi)膜癌細(xì)胞株HEC-1B體外培養(yǎng)后配成懸液注射于裸鼠皮下,建立人子宮內(nèi)膜癌動(dòng)物模型。26只裸鼠均造模成功,為提高準(zhǔn)確性,去掉瘤體結(jié)節(jié)最大及最小的兩只,其余實(shí)驗(yàn)荷瘤裸鼠隨機(jī)地分為四組,標(biāo)記為低、中、高劑量治療組及對(duì)照組,對(duì)照組肌注生理鹽水用于對(duì)照,治療組肌注丙氨瑞林進(jìn)行實(shí)驗(yàn),分別按20ug/kg、40ug/kg、80ug/kg的劑量計(jì)算用藥量。一次/日,連續(xù)治療4周。實(shí)驗(yàn)期間密切觀察一般情況,定期測(cè)量移植瘤體積,繪制腫瘤生長(zhǎng)曲線,判定丙氨瑞林抑制腫瘤情況；實(shí)驗(yàn)結(jié)束時(shí)處死裸鼠,完整剔出裸鼠皮下移植瘤,稱得瘤重,并計(jì)算抑瘤率,然后將各組每塊瘤組織分為兩份,一份用來(lái)HE染色,觀察移植瘤細(xì)胞病理變化；另一份用于免疫組化檢測(cè)PinX1蛋白的表達(dá)情況。 實(shí)驗(yàn)結(jié)果 1、腫瘤開(kāi)始生長(zhǎng)及藥物干預(yù)初期,裸鼠一般情況好,反應(yīng)佳。隨著腫瘤的逐漸增大,各實(shí)驗(yàn)組裸鼠均出現(xiàn)消瘦,精神、食欲、活動(dòng)能力均下降,其中丙氨瑞林高劑量組在實(shí)驗(yàn)后期表現(xiàn)最明顯的。 2、經(jīng)過(guò)4周干預(yù)后,各干預(yù)組移植瘤的體積分別是：低劑量組1367.3±111.56mm3、中劑量組1123±117.4mm3、高劑量組982±97.1mm3,與對(duì)照組1622.8±154.4mm3相比,有顯著性差異(P0.01),低劑量組的抑瘤率為15.72%、中劑量組的抑瘤率為30.76%、高劑量組的抑瘤率為39.46%,中、高劑量組之間的比較瘤體體積和抑瘤率均無(wú)顯著差異(p=0.056),其他組間比較差異明顯(P0.05)。 3、光鏡下見(jiàn)對(duì)照組間質(zhì)減少,細(xì)胞增生活躍,形態(tài)大小不一,異型性明顯,核大而深染,可見(jiàn)核分裂象,核漿比例失調(diào),丙氨瑞林治療組細(xì)胞腫脹,異型性小,可見(jiàn)核皺縮、裂解、凋亡、壞死細(xì)胞。并可見(jiàn)大片壞死區(qū)。 4、對(duì)照組中移植瘤組織中PinX1表達(dá)極少或缺如,各干預(yù)組表達(dá)均增高,與對(duì)照組比較差異顯著(P0.05),,各干預(yù)組中,低劑量組表達(dá)最低；高劑量組表達(dá)最強(qiáng),兩兩相比較,僅中高劑量組之間無(wú)顯著差異(P0.05)。 研究結(jié)論： 1、丙氨瑞林能夠直接抑制子宮內(nèi)膜癌裸鼠移植瘤的生長(zhǎng),在一定范圍內(nèi)其抑制作用與丙氨瑞林劑量呈正相關(guān)。 2、丙氨瑞林可使移植瘤細(xì)胞出現(xiàn)明顯的病理改變。 3、丙氨瑞林可能是通過(guò)上調(diào)腫瘤細(xì)胞中PinX1的表達(dá),抑制端粒酶活性,使腫瘤細(xì)胞端粒得不到延伸,從而實(shí)現(xiàn)抑瘤目的。
[Abstract]:Research purposeGonadotropin releasing hormone analogue has been used in the treatment of many kinds of tumors, but its mechanism remains to be studied.In this study, we investigated the effects of different doses of alarelin on growth inhibition and PinX1 expression in nude mice with endometrial carcinoma.To explore the possible mechanism of the effect of gonadotropin releasing hormone analogues on the inhibition of tumor growth by telomerase-stimulated tumor pathway.Research methodHuman endometrial carcinoma cell line HEC-1B was cultured in vitro and injected into nude mice subcutaneously. The animal model of human endometrial carcinoma. 26 nude mice were established successfully. In order to improve the accuracy, the two largest and smallest tumor nodules were removed.The other experimental nude mice were randomly divided into four groups: low, medium and high dose treatment group and control group. The control group was intramuscularly injected with normal saline for the control group, and the treatment group was intramuscularly injected with alarelin. The dosage of the drug was calculated according to the dosage of 20ugr / kg ~ 40ugr / kg / kg ~ 80ugr / kg respectively.Once a day for 4 weeks.During the experiment, we observe the general situation closely, measure the volume of the transplanted tumor regularly, draw the tumor growth curve, and judge the inhibition of the tumor by alarelin. At the end of the experiment, we killed the nude mice, completely removed the transplanted tumor under the skin of the nude mice, and weighed the tumor.The tumor inhibition rate was calculated, then each tumor tissue was divided into two parts, one was used for HE staining to observe the pathological changes of transplanted tumor cells, the other was used to detect the expression of PinX1 protein by immunohistochemistry.Experimental results1. At the beginning of tumor growth and drug intervention, nude mice were generally in good condition and good response.With the increase of tumor, the weight loss, spirit, appetite and activity of the nude mice in each experimental group were all decreased, especially in the high dose group of alarelin in the late stage of the experiment.2. After 4 weeks of intervention, the volume of transplanted tumor in each intervention group was 1367.3 鹵111.56 mm 3 in low dose group, 1123 鹵117.4 mm 3 in middle dose group and 982 鹵97.1mm 3 in high dose group, compared with 1622.8 鹵154.4mm3 in control group.There was significant difference in tumor inhibition rate between low dose group (15.72%), middle dose group (30.76%) and high dose group (39.46%). There was no significant difference in tumor volume and tumor inhibition rate between middle and high dose groups (P 0.056).3. Under the light microscope, the interstitial cells of the control group were decreased, the cells proliferated and active, the size of the cells varied, the heterogeneity was obvious, the nucleus was large and deep stained, the mitotic image was seen, the proportion of nuclear and cytoplasm was disordered, the cells in the treatment group were swollen, the dysplasia was small, and the nucleus shrank.Lytic, apoptotic, necrotic cells.A large area of necrosis can be seen.(4) the expression of PinX1 in transplanted tumor tissues in the control group was very little or absent, and the expression of PinX1 in each intervention group was higher than that in the control group, the difference was significant (P 0.05). The expression of PinX1 was the lowest in the low dose group, the strongest in the high dose group, and the highest in both groups.There was no significant difference between middle and high dose groups (P 0.05).The study concluded that:1. Alarelin could directly inhibit the growth of endometrial carcinoma xenografts in nude mice, and the inhibitory effect was positively correlated with the dose of alamrelin in a certain range.2, alarelin could cause obvious pathological changes in transplanted tumor cells.3. Alarelin may inhibit telomerase activity by upregulating the expression of PinX1 in tumor cells, resulting in no extension of telomere in tumor cells, so as to achieve the purpose of tumor inhibition.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.31

【參考文獻(xiàn)】

相關(guān)期刊論文 前8條

1 張玉泉;GnRH-A作用于卵巢腫瘤的研究[J];國(guó)外醫(yī)學(xué).婦產(chǎn)科學(xué)分冊(cè);1997年01期

2 朱軍;丁建強(qiáng);馮云;;端粒、端粒酶研究及應(yīng)用進(jìn)展[J];中國(guó)醫(yī)藥科學(xué);2012年07期

3 劉石萍;楊佳欣;;促性腺激素釋放激素類似物在婦科惡性腫瘤中的應(yīng)用[J];國(guó)際婦產(chǎn)科學(xué)雜志;2012年05期

4 李晉芳;廖建興;;端粒酶及端粒酶抑制劑的研究[J];口腔頜面外科雜志;2007年03期

5 衛(wèi)旭東;何健;;端粒和端粒酶與腫瘤干細(xì)胞的研究現(xiàn)狀[J];中華腫瘤防治雜志;2011年09期

6 顏芹;齊元富;;端粒酶與腫瘤[J];深圳中西醫(yī)結(jié)合雜志;2011年04期

7 孫潔;譚亞敏;黃河;朱園園;藍(lán)建平;來(lái)曉瑜;;白血病細(xì)胞中端粒酶抑制因子Pinx1的表達(dá)與端粒酶活性關(guān)系的研究[J];中國(guó)病理生理雜志;2006年09期

8 付強(qiáng),朱理瑋,王鵬志;內(nèi)源性端粒酶抑制基因在大腸癌中的表達(dá)及臨床研究[J];中華普通外科雜志;2004年03期

，

本文編號(hào)：1762582