| 许林波,梁丽斯,王 蓓,邓晓红,白昌民.血浆M-CSF、MMP9、TIMP-1水平及HPV阳性大鼠宫颈癌增殖能力的关系研究[J].,2022,(8):1439-1443 |
| 血浆M-CSF、MMP9、TIMP-1水平及HPV阳性大鼠宫颈癌增殖能力的关系研究 |
| Study on the Relationship between Plasma Levels of M-CSF, MMP9, TIMP-1 and Cervical Cancer Proliferation in HPV-positive Rats |
| 投稿时间：2021-08-24 修订日期：2021-09-20 |
| DOI：10.13241/j.cnki.pmb.2022.08.008 |
| 中文关键词: 宫颈癌 HPV 巨噬细胞集落刺激因子 基质金属蛋白酶9 基质金属蛋白酶组织抑制因子1 增殖 |
| 英文关键词: Cervical cancer HPV M-CSF MMP9 TIMP-1 Proliferation |
| 基金项目:陕西省重点研发计划项目（2018SF-068） |
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| 中文摘要: |
| 摘要 目的：探究血浆巨噬细胞集落刺激因子（Macrophage colony stimulating factor, M-CSF）、基质金属蛋白酶9（Matrix metalloproteinase 9, MMP9）及其组织抑制因子1（tissue inhibitor of the metalloproteinases, TIMP1）水平及人乳头瘤病毒（Human papilloma virus，HPV）阳性大鼠宫颈癌增殖能力的关系。方法：20只健康雌性Wistar白化大鼠根据实验目的分为两组：对照组（异种移植时注射SiHa细胞作为对照实验，n=10）和观察组（将转染sh-M-CSF、sh-MMP9和sh-TIMP-1的SiHa细胞注射大鼠的子宫颈，n=10）。通过ELISA测定大鼠血浆M-CSF、MMP9和TIMP-1的水平。通过PCR检测实验大鼠中M-CSF、MMP9和TIMP-1的mRNA表达。使用数字游标卡尺分析大异种移植大鼠肿瘤体积生长。第3、4、5周分别处死并切除大鼠肿瘤进行称重。通过免疫组织化学分析肿瘤组织中增殖细胞核抗原（Proliferating cell nuclear antigen，PCNA）、pAKT和pSTAT3的蛋白表达。通过免疫组织化学染色和TUNEL染色分别确定Ki67阳性细胞数量及凋亡细胞数量。结果：观察组较对照组M-CSF、MMP9和TIMP-1的水平降低（P<0.05）。观察组较对照组M-CSF、MMP9和TIMP-1的mRNA表达降低（P<0.05）。随着时间的增加，两组大鼠肿瘤体积均增加。1周和2周对照组和观察组大鼠肿瘤体积比较无差异（P>0.05），第3周、第4周和第5周，观察组较对照组大鼠肿瘤体积降低（P<0.05）。观察组较对照组大鼠体内肿瘤重量减少（P<0.05）。观察组较对照组PCNA、pAKT和pSTAT3的蛋白表达量降低（P<0.05）。观察组较对照组Ki67 阳性细胞数量降低，凋亡细胞升高（P<0.05）。结论：降低血浆M-CSF、MMP2和TIMP1水平可促进HPV阳性大鼠宫颈癌细胞凋亡，有效抑制细胞增殖。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the relationship between the levels of plasma M-CSF, MMP9, TIMP-1 and the proliferation of cervical cancer in HPV-positive rats. Methods: Twenty healthy female Wistar albino rats were divided into two groups according to the purpose of the experiment: the control group (injecting SiHa cells during xenotransplantation as a control experiment, n=10) and the observation group (the SiHa cells transfected with sh-M-CSF, sh-MMP9 and sh-TIMP-1) Inject into the cervix of rats, n=10). The plasma levels of M-CSF, MMP9 and TIMP-1 were determined by ELISA. The mRNA expression of M-CSF, MMP9 and TIMP-1 in experimental rats was detected by PCR. The digital vernier caliper was used to analyze the tumor volume growth of large xenograft rats. At the 3rd, 4th, and 5th week, the rats were sacrificed and the tumors were excised and weighed. The protein expression of Proliferating cell nuclear antigen (PCNA), pAKT and pSTAT3 in tumor tissues was analyzed by immunohistochemistry. The number of Ki67-positive cells and the number of apoptotic cells were determined by immunohistochemical staining and TUNEL staining, respectively. Results: Compared with the control group, the observation group had lower levels of M-CSF, MMP9 and TIMP-1(P<0.05). The mRNA expression of M-CSF, MMP9 and TIMP-1 in the observation group was lower than that in the control group (P<0.05). With the increase of time, the tumor volume of the two groups of rats increased. There was no difference in tumor volume between the control group and the observation group at 1 week and 2 weeks(P>0.05). At the 3rd, 4th and 5th week, the observation group had a lower tumor volume than the control group (P<0.05) . The observation group had less tumor weight than the control group (P<0.05). The protein expression of PCNA, pAKT and pSTAT3 in the observation group was lower than that in the control group (P<0.05). Compared with the control group, the number of Ki67-positive cells in the observation group decreased, and the number of apoptotic cells increased (P<0.05). Conclusion: Decreasing the levels of plasma M-CSF, MMP2 and TIMP1 can promote the apoptosis of HPV-positive rat cervical cancer cells and effectively inhibit cell proliferation. |
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