中文摘要：

目的研究微小RNA-451（miR-451）通过调控基质金属蛋白酶（MMP）-2和MMP-9的表达对LN229胶质瘤细胞株侵袭能力的影响。方法体内、外实验均设立3组，分别为空白对照组、无义序列组和miR451 mimics组。合成寡核苷酸miR451 mimics转染LN229胶质瘤细胞以上调miR451的表达，采用实时定量PCR检测转染后miR-451的表达，以Western blot方法检测各组MMP-2和MMP-9蛋白的表达，通过Transwell实验评估各组LN229胶质瘤细胞的侵袭能力。同时建立LN229细胞荷瘤裸鼠模型，绘制肿瘤生长曲线，并采用免疫组化方法检测各组肿瘤内MMP-2和MMP-9蛋白的表达。结果PCR检测结果提示，与空白对照组、无义序列组相比，miR451 mimics组miR451的表达明显升高（均P〈0．05）。Western blot结果显示，miR451 mimics组MMP-2的相对表达量（0．26±0．03）均低于空白对照组（0．67±0．07）和无义序列组（0．65±0．04）（均P〈0．05）；miR-451 mimics组MMP-9的相对表达量（0．25±0．02）亦低于空白对照组（0．71±0．04）和无义序列组（0．73±0．01）（均P〈0．05）。Transwell实验结果显示，miR-451 mimics组穿过Transwell小室的细胞数为（41．0±2．9）个，低于空白对照组[（79．0±2．7）个]和无义序列组[（73．0±3．4）个]（均P〈0．05）。体内实验结果表明，miR-451mimics组的肿瘤体积[（697．31±65．25）mm^3]明显小于空白对照组[（1753．69±76．52）mm^3]和无义序列组[（1532．64±65．31）mm^3]（均P〈0．05）；免疫组化结果表明，与空白对照组和无义序列组相比，miR451 mimics组肿瘤组织MMP-2、MMP-9蛋白表达显著降低（均P〈0．05）。结论miR-451通过调控MMP-2和MMP-9的表达抑制LN229胶质瘤细胞的侵袭性生长能力，可能为潜在的人脑胶质瘤基因治疗的候选靶点。

英文摘要：

Objective To study the effect of microRNA-451 （ miR451 ） on invasion ability of LN229 glioma cells line through the regulation of the expression levels of matrix metalloproteinases （MMP） -2 and MMP-9. Methods Both in vivo and in vitro experiments there are 3 groups, they were blank control groups, scramble sequence groups, and miR-451 mimics groups, respectively. The synthetic oligonucleotide miR-451 mimics were transfected into LN229 glioma cells in order to upregulate the expression of miR451. Real-time quantitative PCR assay was used to detect the expression of miR451 after transfection. Western blot was used to detect the expression levels of MMP-2 and MMP-9 proteins. Transwell assay was used to detect the invasion ability of LN229 glioma cells in each group. A LN229 cell tumor-bearing nude mice model was induced at the same time. Tumor growth curve was drawn, and immunohistochemistry was used to detect the expression levels of MMP-2 and MMP-9 proteins in tumors of each group. Results The results of PCR detection suggested that the miR-451 expression was increased significantly in the miR-451 mimics group compared with the blank control group and the scramble sequence group （ all P 〈 0.05 ）. The results of Western blot assay showed that the relative expression levels of MMP-2 in the miR-451 mimics group （ 0. 26 ± 0.03 ） was lower than 0.67 ± 0.03 and 0.65 ± 0.04 respectively in the blank control group and the scramble sequence group （all P 〈0.05）. The relative expression of MMP-9 （0.25 ±0.02） in the miR451 mimics group was lower than 0.71 ±0.04, and 0.73 ±0.01 in the blank control group and the scramble sequence group （all P 〈 0.05 ）. The results of Transwell assay showed that the number of cells passing through Transwell chamber in the miR-451 mimics group was 41.0 ± 2.9, it was lower than 79.0 ± 2.7 in the blank control group and 73.0 ± 3.4 in the scramble sequence group （ all P 〈 0. 05 ）. The results of in vivo experiment showed that the tumor volume （697.