本文選題：CD39 + 血管瘤��； 參考：《瀘州醫(yī)學(xué)院》2013年碩士論文

【摘要】：目的：建立嬰幼兒增殖期血管瘤的裸鼠模型，探討CD39在普萘洛爾治療增殖期血管瘤中的作用機(jī)制。方法：將在手術(shù)室無(wú)菌條件下手術(shù)切除的嬰幼兒增生期毛細(xì)血管瘤新鮮標(biāo)本，均勻切成小塊（約3.0mm×3.0mm×3.0mm）移植入實(shí)驗(yàn)裸鼠臀背部皮下，每只皮下移植兩個(gè)瘤體組織，建立嬰幼兒血管瘤的裸鼠異種移植的動(dòng)物實(shí)驗(yàn)?zāi)Ｐ�。在移�?5天后，將移植組織均成活的60只的實(shí)驗(yàn)荷瘤裸鼠進(jìn)行隨機(jī)對(duì)照分組實(shí)驗(yàn)，隨機(jī)分為兩個(gè)實(shí)驗(yàn)小組：組A（普萘洛爾治療組），組B（生理鹽水對(duì)照組），每組30只。無(wú)菌條件下，分別給予普萘洛爾溶液和生理鹽水灌胃進(jìn)行干預(yù)，隔日一次。在首次給予藥物治療前、治療后7天、14天、21天、28天，使用頸椎脫臼法，分批將實(shí)驗(yàn)裸鼠處死，每次每組隨機(jī)處死6只，切取瘤體組織。用游標(biāo)卡尺分別測(cè)量?jī)山M實(shí)驗(yàn)裸鼠移植瘤橫徑b的和最大直徑a,并根據(jù)公式V=π／6×a×b2估算腫瘤體積變化情況；將切取的瘤體組織石蠟包埋，制成切片，進(jìn)行HE染色，分析瘤體組織特點(diǎn)，同時(shí)進(jìn)行免疫組織化學(xué)染色，檢測(cè)組織的CD39、Caspase-3和Ki-67的表達(dá)；TUNEL法檢測(cè)移植瘤組織中的細(xì)胞凋亡情況；采用Pearson相關(guān)分析法進(jìn)行CD39表達(dá)光密度值與細(xì)胞凋亡的相關(guān)性分析；酶聯(lián)免疫吸附法（ELISA）檢測(cè)移植瘤組織的ATP濃度；所有的實(shí)驗(yàn)數(shù)據(jù)統(tǒng)計(jì)學(xué)分析使用SPSS19.0統(tǒng)計(jì)軟件進(jìn)行。結(jié)果：治療前，各組的實(shí)驗(yàn)裸鼠的血管瘤組織都生長(zhǎng)良好，組間瘤體的體積無(wú)顯著差異（P＞0.05）。治療后7天、14天，生理鹽水對(duì)照組的血管瘤瘤體體積繼續(xù)生長(zhǎng)、增大，而普萘洛爾治療組血管瘤瘤體體積明顯小于生理鹽水對(duì)照組（P0.01）。干預(yù)后21天、28天，普萘洛爾治療組瘤體進(jìn)一步縮小，較前更加明顯，而生理鹽水組裸鼠瘤體也開始不同程度的縮小，但是幅度較小。在鏡下觀測(cè)瘤體標(biāo)本HE染色切片，普萘洛爾治療組瘤體組織血管減少、破壞，管間纖維脂肪組織浸潤(rùn)，血管內(nèi)皮細(xì)胞分散、稀疏、萎縮，血管壁塌陷、變形，，管腔有閉塞、破壞征象；而生理鹽水對(duì)照組血管瘤瘤體組織毛細(xì)血管豐富，密集，未見管腔和血管壁有萎縮、破壞征象。普萘洛爾治療組的CD39光密度（MD）和Ki-67的陽(yáng)性指數(shù)與生理鹽水對(duì)照組相比均有減少，兩組間有顯著差異性（P0.05）。普萘洛爾治療組的Caspase3和細(xì)胞凋亡指數(shù)明顯高于生理鹽水組，兩組間有顯著差異性（P0.01）；ELISA法檢測(cè)ATP濃度，顯示普萘洛爾治療組高于生理鹽水對(duì)照組，兩組之間有顯著差異性（P0.05）。 CD39表達(dá)與瘤體細(xì)胞凋亡呈負(fù)相關(guān)（r=-0.649,P0.01）。結(jié)論：1.普萘洛爾可促進(jìn)嬰幼兒增生期血管瘤裸鼠模型中的瘤體消退。2.普萘洛爾對(duì)增生期血管瘤的治療機(jī)制與血管瘤內(nèi)皮細(xì)胞上CD39的表達(dá)變化有關(guān)�？赡芷渫ㄟ^降低CD39對(duì)ATP的降解能力，發(fā)揮ATP的細(xì)胞毒性作用，從而促使瘤體細(xì)胞凋亡，達(dá)到治療作用。
[Abstract]:Objective: to establish a nude mouse model of infantile proliferative hemangioma and explore the mechanism of CD39 in propranolol in the treatment of proliferative hemangioma. Methods: a fresh specimen of neonatal hyperplastic capillary hemangioma was removed under aseptic conditions in the operation room and cut into a small block (about 3.0mm x 3.0mm x 3.0mm) and transplanted into the hip back of nude mice Subcutaneous, each subcutaneous transplantation of two tumor tissues to establish an experimental model of xenotransplantation in nude mice of infantile hemangioma. After 45 days of transplantation, 60 experimental tumor bearing nude mice were randomly divided into two experimental groups: group A (propranolol treatment group) and group B (saline control) Group 30. Under aseptic conditions, propranolol and saline were given to the stomach for intervention, once every other day. Before the first drug treatment, 7 days, 14 days, 21 days, 28 days after the treatment, the experimental nude mice were executed in batches, and 6 rats were killed each time, and the tissues were measured with vernier calipers. The two groups tested the transverse diameter of B and the largest diameter of a in nude mice. According to the formula V= pi / 6 x a x B2, the tumor volume changes were estimated. The cut tumor tissues were embedded in paraffin, made into slices, stained with HE, and analyzed the tissue characteristics of the tumor. At the same time, immunohistochemical staining was carried out to detect the expression of CD39, Caspase-3 and Ki-67 in the tissue; TUNEL The apoptosis of the transplanted tumor tissue was detected by the method of Pearson correlation analysis. The correlation analysis between the CD39 expression of light density and the apoptosis was analyzed; the ATP concentration of the transplanted tumor tissue was detected by enzyme linked immunosorbent assay (ELISA); all the experimental data were statistically analyzed using SPSS19.0 software. Results: before treatment, each The hemangioma tissue of the experimental nude mice grew well, and there was no significant difference in the volume between the groups (P > 0.05). The volume of hemangioma in the saline control group continued to grow and increase on the 7 day after treatment, and the volume of the hemangioma in the propranolol group was significantly smaller than that of the saline control group (P0.01). The prognosis of the propranolol group was 21 days, 28 days, and proprannaphthalene after the treatment. The tumor in the group of lol treatment was further narrowed and more obvious than before, but the tumor body of nude mice in the saline group began to shrink in varying degrees, but the range was smaller. The HE staining section of the tumor specimen under the microscope showed that the tumor tissue of the propranolol group was reduced, damaged, intertubular fibrous tissue infiltration, vascular endothelial cells dispersed, sparsely and wilted. Contraction, vascular wall collapse, deformation, occlusion of the lumen, destruction of the signs, while the physiological saline control group hemangioma capillary rich, dense, no lumen and vascular wall atrophy, damage signs, the CD39 light density (MD) and Ki-67 in the propranolol group were less than the normal saline control group, and the two groups showed a significant decrease. The Caspase3 and apoptosis index of propranolol group were significantly higher than that of the normal saline group (P0.05). The two groups were significantly different (P0.01), and the ELISA method was used to detect ATP concentration, which showed that the propranolol group was higher than the normal saline control group, and there was a significant difference between the two groups (P0.05). The expression of CD39 was negatively correlated with the apoptosis of the tumor cells. (r=-0.649, P0.01). Conclusion: 1. propranolol can promote the elimination of tumor in the nude mice model of hyperplastic hemangioma. The therapeutic mechanism of.2. propranolol is related to the expression of CD39 on the endothelial cells of hemangioma. It may play a cytotoxic effect of ATP by reducing the ability to reduce CD39 to ATP and thus promote the cytotoxicity of ATP. The apoptosis of the tumor cells can achieve the therapeutic effect.
【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R-332;R732.2

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