右旋柠烯对小鼠胃癌COX-2表达及淋巴管生成的影响

目的探讨右旋柠烯对胃癌组织中淋巴管的生长以及环氧化酶-2（COX-2）表达的影响,为癌的防治提供形态学依据。方法将50只昆明小鼠用致癌剂苯并芘（B（a）P）灌胃12周构建小鼠胃癌模型。确定胃癌形成之后将其随机分成治疗组（n=25）、对照组（n=25）。治疗组用5%右旋柠烯灌胃干预;对照组用等量色拉油灌胃。另选取10只昆明小鼠用等量色拉油灌胃作为正常组（n=10）。第24周取材,测量肿瘤体积。采用HE染色观察癌组织的生长、浸润;免疫组织化学S-P法分析COX-2和淋巴管内皮细胞透明质酸受体-1（LYVE-1）在各组组织及淋巴管中的表达。结果治疗组肿瘤发生率为52%低于对照组的82%（P〈0.05）,其肿瘤体积亦小于对照组（0.758±0.33）cm^3比（2.124±0.29）cm^3,P〈0.05]。光镜下HE染色可见正常胃壁的层次结构被癌组织破坏,并有大量炎性细胞浸润,对照组癌细胞侵袭范围广而深,多达肌层;治疗组侵袭范围较小,主要限于黏膜及黏膜下层。免疫组织化学染色治疗组胃癌组织COX-2呈弱阳性表达且低于对照组（39%比78%,P〈0.05）,而对照组较正常组表达明显增高（78%比20%,P〈0.05）。LYVE-1的表达符合毛细淋巴管的典型形态特征,治疗组胃癌周边组织微淋巴管与对照组相比管腔较小,微淋巴管密度（LMVD）较少,但与正常组比较明显增多（均P〈0.05）。结论右旋柠烯对肿瘤生长有抑制作用,可降低瘤细胞COX-2的表达并影响淋巴管生成;LMVD和COX-2的阳性表达率均与胃癌的生长浸润有关。

Effects of D-Limonene on COX-2 Expression and Lymphangiogenesis in a Mouse Model of Gastric Carcinoma

Objective To investigate the effects of D-limonene on cycloxygenase-2（ COX-2） expression and lymphangiogenesis in gastric carcinoma,and to provide a morphological basis for the prevention and treatment of gastric carcinoma. Methods A mouse model of gastric carcinoma was established by intragastric administration of benzo-a-pyrene for 12 weeks. Fifty mice with gastric carcinoma were intragastrically given either 5% D-limonene（ treatment group,n = 25） or the same amount of salad oil（ control group,n = 25）. In addition,10 normal mice were given the same amount of salad oil（ normal group）. The tumor volume was measured at 24 weeks after treatment. The tumor growth and infiltration were observed by HE staining. The expression of COX-2 and lymphatic vessel endothelial hyaluronan receptor（ LYVE-1） in gastric cancer tissues or lymphatic vessels was detected by immunohistochemistry. Results The tumor incidence in treatment group was lower than that in control group（ 52% vs 82%,P〈0. 05）. Furthermore,the tumor volume in treatment group was less than that in control group（（ 0. 758 ± 0. 33） cm^3vs（ 2. 124 ± 0. 29） cm^3,P〈0. 05）. The destroyed hierarchical structure of normal gastric wall and obvious infiltration of inflammatory cells were observed under optical microscope in mice with gastric carcinoma. In control group,histopathology showed wide and deep invasion of cancer cells to the muscular layer.In treatment group,histopathology showed small range of invasion which was mainly limited to the mucosa and submucosa. Compared with control group,the positive rate of COX-2 expression decreased in both treatment group（ 39% vs 78%,P〈0. 05） and normal group（ 20% vs 78%,P〈0. 05）. The expression of LYVE-1 was consistent with the typical morphological characteristics of lymphatic capillaries. The lumen diameter of lymphatic microvessels surrounding tumors in treatment group was smaller than that in control group（ P〈0. 05）. Moreover,the lymphatic microvessel density in treat