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

【摘要】：研究目的 通過(guò)構(gòu)建人子宮內(nèi)膜癌裸鼠皮下移植瘤動(dòng)物模型，探討促性腺激素釋放激素（GnRH）類(lèi)似物——醋酸丙氨瑞林（Alarelin Acetate）對(duì)人子宮內(nèi)膜癌裸鼠移植瘤的生長(zhǎng)及對(duì)Smurf2表達(dá)的影響。使用3種不同劑量的丙氨瑞林對(duì)人子宮內(nèi)膜癌裸鼠移植瘤模型進(jìn)行分組干預(yù)實(shí)驗(yàn)，并探討藥物抑制對(duì)Smurf2表達(dá)調(diào)控的影響。 研究方法 將體外培養(yǎng)凍存的人子宮內(nèi)膜癌Hec-1B細(xì)胞復(fù)蘇置于適當(dāng)?shù)沫h(huán)境中培養(yǎng)，當(dāng)細(xì)胞培養(yǎng)到一定比例時(shí)接種于4-6周齡雌性裸鼠左前肢近腋窩處皮下，構(gòu)建形成皮下移植瘤，成功建模后將24只裸鼠隨機(jī)分組，共4組，每組6只：第1組為對(duì)照組，肌肉注射生理鹽水，第2組為丙氨瑞林低劑量組(14g/kg)，第3組為中劑量組(28g/kg)，第4組為高劑量組(56g/kg)。丙氨瑞林給藥方式為背部肌肉注射，，每只裸鼠根據(jù)體重計(jì)算所需用藥劑量，調(diào)整注射液體量為每只裸鼠注射0.1ml，每日給藥1次，連續(xù)給藥4周。在此期間4天測(cè)量1次裸鼠瘤體的最長(zhǎng)徑與最短徑，計(jì)算瘤體體積，繪制腫瘤生長(zhǎng)曲線、同時(shí)觀察裸鼠整體生長(zhǎng)狀況。治療4周后處死裸鼠，取出移植瘤，計(jì)算不同劑量丙氨瑞林組的抑瘤率。將移植瘤組織制成石蠟切片，進(jìn)行HE染色，在光學(xué)顯微鏡下觀察腫瘤組織形態(tài)學(xué)情況。用免疫組織化學(xué)方法檢測(cè)皮下移植瘤組織中Smurf2蛋白的表達(dá)情況。 實(shí)驗(yàn)結(jié)果 1.對(duì)照組、丙氨瑞林低、中、高劑量組的裸鼠皮下移植瘤生長(zhǎng)曲線斜率依次減小，生長(zhǎng)速度依次減慢，差異有統(tǒng)計(jì)學(xué)意義(P0.05)； 2.藥物干預(yù)4周后，移植瘤體積分別是：對(duì)照組1628±162mm3，低劑量組1368±256mm3、中劑量組1296±307mm3、高劑量組995±213mm3，差異有統(tǒng)計(jì)學(xué)意義(P0.05)。丙氨瑞林低、中、高劑量組的抑瘤率分別15.94%、20.37%、38.86%，組間兩兩比較，差異有統(tǒng)計(jì)學(xué)意義(P0.05)； 3.移植瘤組織HE染色結(jié)果：光學(xué)顯微鏡下觀察可知，對(duì)照組移植瘤組織結(jié)構(gòu)排列紊亂，細(xì)胞體積較小，有明顯異型性，且間質(zhì)少，細(xì)胞核體積和核漿比也明顯增大，分布不均，染色較深，可見(jiàn)較多核分裂像；治療組移植瘤細(xì)胞排列較稀疏，可見(jiàn)多處無(wú)結(jié)構(gòu)的紅染區(qū)，瘤細(xì)胞核深染、固縮。 4.免疫組織化學(xué)結(jié)果：丙氨瑞林可增加Smurf2蛋白在移植瘤組織中表達(dá)水平，并且隨著丙氨瑞林劑量的增加，Smurf2的表達(dá)逐漸增強(qiáng)（P0.05），且組間兩兩比較差異有統(tǒng)計(jì)學(xué)意義（P0.05）。 實(shí)驗(yàn)結(jié)論 1.丙氨瑞林能夠有效抑制人子宮內(nèi)膜癌細(xì)胞株裸鼠皮下移植瘤的生長(zhǎng)，且與劑量效應(yīng)呈正相關(guān)。 2.丙氨瑞林對(duì)人子宮內(nèi)膜癌裸鼠移植瘤的抑制作用可能是通過(guò)上調(diào)Smurf2的表達(dá)來(lái)實(shí)現(xiàn)的。
[Abstract]:Objective to investigate the effects of gonadotropin releasing hormone (GnRH) analogue-Alarelin Acetateon the growth of human endometrial carcinoma in nude mice and the expression of Smurf2 in nude mice. Three different doses of alarelin were used to treat human endometrial carcinoma xenografts in nude mice. To investigate the effect of drug inhibition on the expression and regulation of Smurf2.Methods the cryopreserved human endometrial carcinoma Hec-1B cells were resuscitated in a suitable environment. When the cells were cultured to a certain proportion, they were inoculated subcutaneously in the left forelimb near axilla of 4-6 weeks old female nude mice. After successful modeling, 24 nude mice were randomly divided into 4 groups, 6 in each group: the first group was the control group. Normal saline was injected intramuscularly in the second group, in the low dose group (14 g / kg), in the third group in the middle dose group (28 g / kg), in the fourth group in the high dose group (56 g / kg). Alarelin was injected intramuscularly on the back of each nude mouse according to its body weight. The dosage of the injection was adjusted to 0.1 ml per nude mouse once a day for 4 weeks. The longest and shortest diameters of nude mice tumor were measured once in 4 days, the tumor volume was calculated, the tumor growth curve was drawn, and the whole growth state of nude mice was observed at the same time. After 4 weeks of treatment, nude mice were killed, transplanted tumor was removed and tumor inhibition rate was calculated in different doses of alarelin group. The transplanted tumor tissue was made into paraffin sections and stained with HE, and the morphology of the tumor was observed under optical microscope. The expression of Smurf2 protein in subcutaneous transplanted tumor was detected by immunohistochemical method. In the control group, the slope of growth curve of subcutaneous transplanted tumor decreased in turn, and the growth rate of subcutaneous transplanted tumor in the control group decreased in turn, and the difference was statistically significant (P 0.05). After 4 weeks of drug intervention, the volume of transplanted tumor was 1628 鹵162mm3 in control group, 1368 鹵256mm3 in low dose group, 1296 鹵307mm3 in middle dose group and 995 鹵213mm3 in high dose group. The difference was statistically significant (P 0.05). The tumor inhibition rate of the low, medium and high dose groups was 15.9420.37 and 38.86, respectively. The difference between the two groups was statistically significant (P 0.05; 3. 0. 5%, P < 0. 05; P < 0. 05; P < 0. 05; P < 0. 05; P < 0. 05). The results of HE staining showed that the structure of the transplanted tumor in the control group was disordered, the size of cells was small, there was obvious heterogeneity, and the interstitial size was less, the nuclear volume and the ratio of nucleus to cytoplasm were also increased obviously, and the distribution was uneven. In the treatment group, the transplanted tumor cells were arranged sparsely, and there were many unstructured red staining areas. The nuclei of the treatment group were deep stained and pyknotic. Immunohistochemical results: alarelin could increase the expression of Smurf2 protein in transplanted tumor tissues, and the expression of Smurf2 increased gradually with the increase of the dose of alarelin, and the difference between the two groups was statistically significant (P 0.05). Conclusion 1. Alarelin could effectively inhibit the growth of human endometrial carcinoma cell line in nude mice, and had a positive correlation with dose effect. 2. The inhibitory effect of alarelin on human endometrial carcinoma xenografts in nude mice may be achieved by upregulating the expression of Smurf2.
【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(lèi)號(hào)】：R737.33

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