维生素D3对实验大鼠乳腺增生的影响。
Effect of vitamin D3 on hyperplasia of mammary glands in experimental rats.
作者信息
Song Danfei, Shi Xuejuan, Li Changtian, Cao Xiaolin, Lu Yuanyuan, Li Junlai
机构信息
Department of Ultrasound, The Second Medical Center, Chinese PLA General Hospital, Beijing, China.
Outpatient Department of Fengbei Bridge, Southern Medical District of Chinese PLA General Hospital, Beijing, China.
出版信息
Gland Surg. 2022 Jan;11(1):136-146. doi: 10.21037/gs-21-851.
BACKGROUND
1,25(OH)2D3/vitamin D3 receptor (VD3/VDR) signaling pathway can inhibit the occurrence of breast cancer in many ways. We used vitamin D3 to interfere with Hyperplasia of mammary glands (HMG) model rats, and to explore the intervention effect of vitamin D3 on HMG.
METHODS
We divided 42 female rats into six groups randomly: blank control group, hyperplasia model group, negative control group, and vitamin D3 (VD3) groups of low-dose (LVD, 5 µg/kg), medium-dose (MVD, 10 µg/kg), and high-dose (HVD, 20 µg/kg). We established HMG model in all groups except for the blank control group, then different dose of VD3 was intraperitoneal injected for VD3 groups and normal saline (NS) was given to the negative control group. After the experiment, the body weights, heights and diameters of nipples, and the thickness of the mammary gland of rats were measured. The serum content of sex hormone and VD3 were detected by enzyme-linked immunosorbent assay (ELISA). The tissues of mammary glands were analyzed by hematoxylin and eosin (HE) stain, and the expression of estrogen receptor α (ERα), progesterone receptor (PR), and VDR were detected by immunohistochemical (IHC) stain. Similarly, the total protein expression of ERα, PR, and VDR were measured by western blot.
RESULTS
Compared with the hyperplasia group, rats in the VD3 groups displayed a marked decrease of the thickness of the mammary glands and the height and diameter of the nipples. The serum estrogen (E2), testosterone (T), luteinizing hormone (LH), and VD3 was markedly decreased in all VD3 groups (P<0.05). The IHC results showed that ERα and PR was decreased in all three VD3 groups; however, VDR was increased. Western blot demonstrated that both ERα and PR were reduced in VD3 groups, while the VDR level was significantly enhanced. Overall, the findings suggested that VD3 could be used in HMG treatment.
CONCLUSIONS
Supplementation of VD3 could markedly decrease the mammary gland thickness, nipple diameter, and nipple height of rats, accompanied by the decrease of serum E2, T, and LH. Intervention with VD3 can lead to decreased expression of ERa and PR, in conjunction with the increase of VDR.
背景
1,25(OH)₂D₃/维生素D₃受体（VD₃/VDR）信号通路可通过多种方式抑制乳腺癌的发生。我们使用维生素D₃干预乳腺增生（HMG）模型大鼠，以探讨维生素D₃对HMG的干预作用。
方法
将42只雌性大鼠随机分为六组：空白对照组、增生模型组、阴性对照组以及低剂量（LVD，5 μg/kg）、中剂量（MVD，10 μg/kg）和高剂量（HVD，20 μg/kg）的维生素D₃（VD₃）组。除空白对照组外，其余各组均建立HMG模型，然后对VD₃组腹腔注射不同剂量的VD₃，阴性对照组给予生理盐水（NS）。实验结束后，测量大鼠的体重、乳头高度和直径以及乳腺厚度。采用酶联免疫吸附测定（ELISA）法检测血清性激素和VD₃含量。用苏木精-伊红（HE）染色法分析乳腺组织，并采用免疫组织化学（IHC）染色法检测雌激素受体α（ERα）、孕激素受体（PR）和VDR的表达。同样，通过蛋白质免疫印迹法检测ERα、PR和VDR的总蛋白表达。
结果
与增生组相比，VD₃组大鼠的乳腺厚度以及乳头高度和直径均显著降低。所有VD₃组的血清雌激素（E₂）、睾酮（T）、黄体生成素（LH）和VD₃均显著降低（P<0.05）。免疫组织化学结果显示，所有三个VD₃组的ERα和PR均降低；然而，VDR增加。蛋白质免疫印迹法表明，VD₃组的ERα和PR均减少，而VDR水平显著升高。总体而言，研究结果表明VD₃可用于HMG的治疗。
结论
补充VD₃可显著降低大鼠乳腺厚度、乳头直径和乳头高度，同时血清E₂、T和LH降低。VD₃干预可导致ERα和PR表达降低，同时VDR增加。
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