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氯化镉诱导大鼠前列腺前病变过程中溶血磷脂酸受体 1 的表达及其与细胞增殖、凋亡和血管生成的关系。

Expression of lysophosphatidic acid receptor 1 and relation with cell proliferation, apoptosis, and angiogenesis on preneoplastic changes induced by cadmium chloride in the rat ventral prostate.

机构信息

Histology Laboratory, Institute of Applied Molecular Medicine, Department of Basic Medical Sciences, School of Medicine, CEU-San Pablo University, Madrid, Spain.

出版信息

PLoS One. 2013;8(2):e57742. doi: 10.1371/journal.pone.0057742. Epub 2013 Feb 22.

Abstract

BACKGROUND

Lysophosphatidic acid (LPA) is a phospholipid growth factor involved in cell proliferation, differentiation, migration, inflammation, angiogenesis, wound healing, cancer invasion, and survival. This study was directed to evaluate the immunoexpression of LPA-1, cell proliferation, apoptosis, and angiogenesis markers in preneoplastic lesions induced with cadmium chloride in rat prostate.

METHODS

The following parameters were calculated in ventral prostate of normal rats and rats that received Cd in drinking water during 24 months: percentages of cells immunoreactive to LPA-1 (LILPA1), PCNA (LIPCNA), MCM7 (LIMCM7), ubiquitin (LIUBI), apoptotic cells (LIAPO), and p53 (LIp53); volume fraction of Bcl-2 (VFBcl-2); and length of microvessels per unit of volume (LVMV/mm3). Data were analyzed using Student's t-test and Pearson correlation test.

RESULTS

The LILPA1 in dysplastic lesions and normal epithelium of Cd-treated rats was significantly higher than those in the control group. Markers of proliferation were significantly increased in dysplastic lesions, whereas some apoptotic markers were significantly decreased. No significant differences between groups were found in VFBcl-2. Dysplastic lesions showed a significant increase of LIp53. The length of microvessels per unit of volume was elevated in dysplastic acini. Statistically significant correlations were found only between LILPA1 and LIUBI.

CONCLUSIONS

Our results suggest that LPA-1 might be implicated in dysplastic lesions induced by cadmium chloride development. More studies are needed to confirm its potential contribution to the disease.

摘要

背景

溶血磷脂酸(LPA)是一种参与细胞增殖、分化、迁移、炎症、血管生成、伤口愈合、癌症侵袭和存活的磷脂生长因子。本研究旨在评估氯化镉诱导的大鼠前列腺癌前病变中 LPA-1、细胞增殖、细胞凋亡和血管生成标志物的免疫表达。

方法

计算正常大鼠和在饮用水中接受 Cd 处理 24 个月的大鼠前列腺腹侧的以下参数:对 LPA-1(LILPA1)、PCNA(LIPCNA)、MCM7(LIMCM7)、泛素(LIUBI)、凋亡细胞(LIAPO)和 p53(LIp53)有免疫反应的细胞百分比;Bcl-2 的体积分数(VFBcl-2);和每单位体积的微血管长度(LVMV/mm3)。使用 Student's t 检验和 Pearson 相关检验分析数据。

结果

Cd 处理大鼠的发育不良病变和正常上皮中的 LILPA1 明显高于对照组。增殖标志物在发育不良病变中显著增加,而一些凋亡标志物则显著减少。VFBcl-2 各组间无显著差异。发育不良病变中 LIp53 明显增加。单位体积的微血管长度在发育不良的腺泡中升高。仅在 LILPA1 和 LIUBI 之间发现有统计学意义的相关性。

结论

我们的结果表明,LPA-1 可能参与了氯化镉诱导的发育不良病变的发生。需要进一步的研究来证实其对疾病的潜在贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ab9/3579784/8c5f3278a835/pone.0057742.g001.jpg

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