Zhang Cui-cui, Li Kai, Wei Xi-yin, Chen Cheng, Yuan Jing, Wang Jing
Department of Thoracic Oncology, Cancer Institute and Hospital of Tianjin Medical University, China.
Zhonghua Zhong Liu Za Zhi. 2011 Jun;33(6):415-20.
To compare the effect of rh-endostatin on micrangium in tumor and myocardial tissue in nude mice.
Nude mice were randomized into 4 groups (10 mice in each group), blank control group (without tumor burden, received NS 100 µl×d(-1) injection), drug control group (without tumor burden, received rh-endostatin 400 µg×d(-1) injection), model group (with tumor burden, received NS 100 µl×d(-1) injection) and treatment group (with tumor burden, received rh-endostatin 400 µg×d(-1) injection) for 28 days. The tumor volume and body weight of the mice were measured before and after administration. The expression of CD34, MMP-2, MMP-9, HIF-1α and VEGF in the myocardium and tumor were detected by immunohistochemistry. The vascular structure was observed by immunoenzymatic CD34 and Masson double staining.
The increase of tumor volume of the treatment group [(48.18 ± 37.31) mm(3)] was significantly lower than that in the model group [(113.80 ± 73.27) mm(3)). The changes of body weight was not significant different among the four groups. After treated with rh-endostatin, the expressions of MMP-9 and VEGF in tumors were significantly down-regulated, but the expressions of MMP-2 and HIF-1α in the tumor were not. The microvessel density (MVD) in the tumors of treatment group was significantly decreased compared with that of model group. The proportion of tumor vessels covered by collagen in the treatment group was increased compared with that of the model group. However, MVD and micrangium in myocardium were not changed significantly.
Rh-endostatin can decrease the expression of MMP-9, VEGF and MVD, inhibit the tumor growth and normalize tumor micrangium in tumor but not weaken the MMPs and MVD of mature micrangium in myocadium.
比较重组人血管内皮抑素（rh-endostatin）对裸鼠肿瘤组织和心肌组织微血管的影响。
将裸鼠随机分为4组（每组10只），空白对照组（无肿瘤负荷，每日注射100 μl生理盐水）、药物对照组（无肿瘤负荷，每日注射400 μg rh-endostatin）、模型组（有肿瘤负荷，每日注射100 μl生理盐水）和治疗组（有肿瘤负荷，每日注射400 μg rh-endostatin），给药28天。给药前后测量小鼠肿瘤体积和体重。采用免疫组织化学法检测心肌和肿瘤组织中CD34、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）的表达。采用免疫酶标CD34和Masson双重染色观察血管结构。
治疗组肿瘤体积增加量[（48.18±37.31）mm³]明显低于模型组[（113.80±73.27）mm³]。四组小鼠体重变化差异无统计学意义。rh-endostatin治疗后，肿瘤组织中MMP-9和VEGF的表达明显下调，但肿瘤组织中MMP-2和HIF-1α的表达未下调。与模型组相比，治疗组肿瘤组织微血管密度（MVD）明显降低。与模型组相比，治疗组肿瘤血管被胶原覆盖的比例增加。然而，心肌组织中的MVD和微血管无明显变化。
rh-endostatin可降低MMP-9、VEGF的表达及MVD，抑制肿瘤生长，使肿瘤微血管正常化，但不削弱心肌成熟微血管的MMPs和MVD。
