【摘要】：目的：探討普萘洛爾對增殖期血管瘤的治療作用及可能機制。方法：將手術切除的嬰幼兒增殖期血管瘤新鮮組織塊移植于裸鼠皮下，建立血管瘤動物模型；在移植后的第45天，將移植瘤組織均成活的22只實驗裸鼠隨機分為2組：組1(普萘洛爾治療組)，組2(生理鹽水對照組)，每組11只，分別灌注普萘洛爾溶液和生理鹽水干預治療，觀察比較移植瘤的生長情況；在首次藥物干預后的第15天，將實驗裸鼠用頸椎脫臼法處死，切取移植的瘤體組織。免疫組化法檢測移植瘤組織中血管內皮細胞MVD值，以及CD34、Ki-67、Bcl-2、VEGF的表達情況，TUNEL法檢測移植瘤組織中細胞凋亡情況；酶聯(lián)免疫吸附法（ELISA）檢測cAMP濃度及PKA活性變化。結果：1.在藥物干預后l周，普萘洛爾組與生理鹽水組移植瘤體積比較，兩組瘤體的體積有明顯差異(P0.05)；在藥物干預后2周，普萘洛爾組移植瘤體積明顯小于生理鹽水組，兩組差異顯著(P0.01)。普萘洛爾組瘤體組織顏色蒼白，血供較差，，體積明顯縮小，質地變硬。生理鹽水組瘤體組織顏色紅潤，血供良好，體積無明顯縮小，較有彈性。光鏡下見，普萘洛爾組瘤體組織以纖維脂肪組織為主，血管內皮細胞稀疏分散，血管壁變形、塌陷，管腔結構有破壞征象；而生理鹽水組瘤體組織毛細血管增生豐富，未見血管壁及管腔結構有破壞征象。2.免疫組化檢測：普萘洛爾組MVD值，CD34、Ki-67、Bcl-2、VEGF的表達均明顯低于生理鹽水組，組間差異明顯(P0.05)；TUNEL法檢測普萘洛爾組細胞凋亡指數(shù)明顯高于生理鹽水組，兩組間差異顯著(P0.01)。3.酶聯(lián)免疫吸附法檢測：普萘洛爾組cAMP濃度和PKA活性明顯低于生理鹽水組，兩組間差異明顯(P0.05)；且普萘洛爾組cAMP濃度和PKA活性變化呈正相關(γ=0.607，P0.01)。結論：1.普萘洛爾對增殖期血管瘤有明顯的治療作用。2.普萘洛爾可誘導血管瘤內皮細胞凋亡，抑制其增殖，促進瘤體消退。3.普萘洛爾可能通過抑制cAMP／PKA信號通路對ERK／MAPK信號通路的激活，從而抑制增殖期血管瘤VEGF的分泌。
[Abstract]:Objective: to investigate the therapeutic effect of propranolol on proliferative hemangioma and its possible mechanism. Methods: the fresh tissue mass of proliferative hemangioma was transplanted into nude mice subcutaneously, and the animal model of hemangioma was established on the 45th day after transplantation. Twenty-two nude mice were randomly divided into two groups: group 1 (propranolol treatment group) and group 2 (saline control group), each group (n = 11) were treated with propranolol solution and saline respectively. At the 15th day after the first drug intervention, the nude mice were killed by cervical dislocations and the transplanted tumor tissues were removed. Immunohistochemical method was used to detect the expression of MVD and CD34,Ki-67,Bcl-2,VEGF in vascular endothelial cells, TUNEL method was used to detect apoptosis, and (ELISA) was used to detect the concentration of cAMP and the activity of PKA. The result is 1: 1. The volume of transplanted tumor in propranolol group was significantly different from that in saline group at 1 week after drug intervention (P0.05), and the volume of transplanted tumor in propranolol group was significantly smaller than that in saline group at 2 weeks after drug intervention. There was a significant difference between the two groups (P0.01). In propranolol group, the tumor tissue was pale in color, poor in blood supply, significantly reduced in volume and hardened in texture. In the saline group, the color of the tumor tissue was ruddy, the blood supply was good, the volume was not obviously reduced, and the tumor tissue was elastic. Under light microscope, the tumor tissue of propranolol group was mainly fibrous adipose tissue, vascular endothelial cells were sparsely dispersed, vascular wall was deformed, collapsed, and the structure of the lumen was damaged, while the normal saline group was rich in capillary hyperplasia. No signs of damage to vascular wall and lumen structure were found. 2. The expression of MVD and CD34,Ki-67,Bcl-2,VEGF in propranolol group was significantly lower than that in saline group, and the difference was significant (P0.05). The apoptosis index of propranolol group was significantly higher than that of normal saline group (P0.05). The difference between the two groups was significant (P0.01). Enzyme linked immunosorbent assay (Elisa) showed that the concentration of cAMP and the activity of PKA in propranolol group were significantly lower than those in saline group (P0.05), and there was a positive correlation between cAMP concentration and PKA activity in propranolol group (緯 = 0.607, P0.01). Conclusion 1. Propranolol has obvious therapeutic effect on proliferative hemangioma. 2. Propranolol can induce endothelial cell apoptosis, inhibit the proliferation of hemangioma, and promote tumor regression. Propranolol may inhibit the secretion of VEGF in proliferative hemangioma by inhibiting the activation of ERK/MAPK signaling pathway by cAMP/PKA signaling pathway.
【學位授予單位】：瀘州醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R739.5

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