实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (6): 587-596.DOI: 10.12300/j.issn.1674-5817.2024.065
• 人类疾病动物模型 • 下一篇
殷玉莲(), 马丽娜, 屠思远, 陈玲, 叶媚娜, 陈红风(
)(
)
收稿日期:
2024-05-08
修回日期:
2024-11-13
出版日期:
2025-01-04
发布日期:
2024-12-25
通讯作者:
陈红风(1964—),女,博士,主任医师,上海市名中医,研究方向:乳腺良恶性疾病的临床及实验研究。E-mail: chhfluk2068@163.com。ORCID:0000-0001-6311-0651作者简介:
基金资助:
YIN Yulian(), MA Lina, TU Siyuan, CHEN Ling, YE Meina, CHEN Hongfeng(
)(
)
Received:
2024-05-08
Revised:
2024-11-13
Published:
2024-12-25
Online:
2025-01-04
Contact:
CHEN Hongfeng (ORCID:0000-0001-6311-0651), E-mail: chhfluk2068@163.com摘要:
目的 通过模拟高催乳素血症及免疫炎症状态,建立非哺乳期乳腺炎(non-puerperal mastitis,NPM)大鼠模型,评价其乳腺局部炎症特征,为乳腺疑难疾病的诊疗研究提供依据。 方法 选用SPF级Wistar雌性大鼠12只,均分为对照组和模型组。实验期间,对照组未接受任何实验性操作和药物处理;模型组连续7 d每日皮下注射1次盐酸甲氧氯普胺注射液100 mg/kg,在注射首日后第10、20、30天分别采用ELISA法检测血清催乳素水平。注射7 d后,将200 μL哺乳期SD母鼠乳汁混合200 μL完全弗氏佐剂制备为油包水乳剂,多点皮下注射至模型组大鼠背部进行首次免疫。首次免疫7 d后,再将油包水乳剂经多点皮下注射至大鼠第3、4、5对乳房进行末次免疫。末次免疫后连续观察乳房外观28 d,计算乳腺结节大小;并于第3、7、14、28天,通过HE染色分析乳腺组织形态学,免疫组织化学法检测CD138表达水平,ELISA法测定乳腺组织中白细胞介素(interleukin,IL)-6、IL-1β、肿瘤坏死因子(tumor necrosis factor,TNF)-α和诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)含量,以综合评价造模情况。 结果 模型组大鼠可见乳腺皮肤破溃,并于破溃处闻及恶臭味,触诊及超声下可见乳腺结节形成。HE染色显示,末次免疫后第3天大鼠乳腺组织中正常导管及小叶结构消失,并见大量浆细胞浸润;第7天可见乳腺导管扩张,导管上皮坏死脱落,管周浆细胞、淋巴细胞(以T淋巴细胞为主)浸润明显;第14天时可见大量纤维脂肪组织、小血管及肉芽组织增生,间质内可见散在浆细胞;第28天时炎性细胞浸润、纤维组织增生现象减轻,肉芽肿形成。大鼠在造模成功后第10天、第20天催乳素水平逐渐升高(P<0.05,P<0.001);模型组大鼠在末次免疫后第3、7、14、28天时,乳腺组织中IL-6和TNF-α含量均较对照组升高(P<0.05);IL-1β含量在末次免疫后第3、7、14天时较对照组升高(P<0.01),第28天时略低于对照组(P>0.05);iNOS在末次免疫后第7天显著高于对照组(P<0.001)。 结论 成功构建大鼠NPM模型,其乳房局部具有肿块、脓肿、溃疡等表现以及乳腺导管扩张和浆细胞浸润的典型病理特征,可为该临床疑难疾病的诊疗研究奠定基础。
中图分类号:
殷玉莲,马丽娜,屠思远,等. 非哺乳期乳腺炎大鼠模型的建立及评价[J]. 实验动物与比较医学, 2024, 44(6): 587-596. DOI: 10.12300/j.issn.1674-5817.2024.065.
YIN Yulian,MA Lina,TU Siyuan,et al. Establishment and Evaluation of a Rat Model of Non-Puerperal Mastitis[J]. Laboratory Animal and Comparative Medicine, 2024, 44(6): 587-596. DOI: 10.12300/j.issn.1674-5817.2024.065.
图1 对照组和模型组大鼠乳腺局部表现和结节大小变化注:A为模型组大鼠造模成功后乳腺外观表现,可观察到多枚结节,局部红肿,部分破溃有脓性分泌物附着。B和C为模型组乳腺超声结果,其中B显示多处扩张的乳腺导管(箭头所示);C显示乳腺组织内炎性结节(箭头所示)。D为对照组的正常乳腺组织表现。E为模型组病理性乳腺结节表现。F为对照组(n=6)和模型组(n=6)在末次免疫后连续观察28 d的乳腺结节大小变化趋势;与对照组比较,d1~d8,***P<0.001;d9~d14,**P<0.01;d15~d28,*P<0.05。
Figure 1 Comparison of local mammary changes and nodule size in control and model groups of ratsNote:A represents the appearance of the mammary gland in the model group after successful modeling, where multiple nodules are observed, with local redness and swelling, and some ulcerations with purulent discharge. B and C represent the ultrasonography results of the mammary gland in the model group, where B shows multiple dilated mammary ducts (indicated by arrows), and C displays inflammatory nodules within the mammary tissue (indicated by arrows). D represents the normal mammary tissue appearance in the control group. E represents the pathological mammary nodule manifestation in the model group. F represents the trend of changes in the size of mammary nodules over 28 days of observation after the final immunization for both the control group (n=6) and model group (n=6). Compared with the control group, d1-d8, ***P<0.001; d9-d14, **P<0.01; d15-d28, *P<0.05.
图2 对照组与模型组大鼠的催乳素含量比较注:ELISA法检测模型组(n=4)大鼠在注射盐酸甲氧氯普胺后第10天、第20天、第30天的血清催乳素水平。与对照组(n=4)比较,*P<0.05,***P<0.001。
Figure 2 Comparison of prolactin levels in the two groups measured by ELISANote: The prolactin levels were detected by ELISA method on the 10th, 20th, and 30th days after metoclopramide hydrochloride injection in the control group (n=4). Compared with the control group (n=4), *P<0.05, ***P<0.001.
时间节点 Time point | 组别 Group | IL-6 ρ/(pg·mL-1) | IL-1β ρ/(pg·mL-1) | TNF-α ρ/(pg·mL-1) | iNOS c/(μmol·L-1) |
---|---|---|---|---|---|
第3天 Day 3 | 对照组 Control group | 65.10±15.51 | 34.41±1.97 | 235.39±23.00 | 8.74±0.87 |
模型组 Model group | 91.42±5.64*** | 71.45±25.20** | 332.05±16.48*** | 9.04±0.85 | |
第7天 Day 7 | 对照组 Control group | 43.18±16.58 | 34.56±2.18 | 324.54±7.83 | 9.53±1.87 |
模型组 Model group | 68.92±17.70** | 52.44±1.85*** | 364.07±27.15** | 13.95±0.92*** | |
第14天 Day 14 | 对照组 Control group | 59.00±6.71 | 23.56±4.10 | 258.08±34.30 | 9.13±1.67 |
模型组 Model group | 71.14±4.95*** | 43.71±10.05** | 348.70±36.87** | 11.13±1.63 | |
第28天 Day 28 | 对照组 Control group | 51.15±7.70 | 44.66±2.64 | 256.21±39.02 | 11.33±0.84 |
模型组 Model group | 84.76±18.18*** | 40.92±3.41 | 303.89±33.40* | 12.20±0.55 |
表1 对照组与模型组大鼠在末次免疫后4个观察节点的IL-6、IL-1β、TNF-α和iNOS水平比较 (xˉ±s, n=6)
Table 1 Comparison of IL-6, IL-1β, TNF-α, and iNOS levels between the control group and the model group at four observation time points after the final immunization
时间节点 Time point | 组别 Group | IL-6 ρ/(pg·mL-1) | IL-1β ρ/(pg·mL-1) | TNF-α ρ/(pg·mL-1) | iNOS c/(μmol·L-1) |
---|---|---|---|---|---|
第3天 Day 3 | 对照组 Control group | 65.10±15.51 | 34.41±1.97 | 235.39±23.00 | 8.74±0.87 |
模型组 Model group | 91.42±5.64*** | 71.45±25.20** | 332.05±16.48*** | 9.04±0.85 | |
第7天 Day 7 | 对照组 Control group | 43.18±16.58 | 34.56±2.18 | 324.54±7.83 | 9.53±1.87 |
模型组 Model group | 68.92±17.70** | 52.44±1.85*** | 364.07±27.15** | 13.95±0.92*** | |
第14天 Day 14 | 对照组 Control group | 59.00±6.71 | 23.56±4.10 | 258.08±34.30 | 9.13±1.67 |
模型组 Model group | 71.14±4.95*** | 43.71±10.05** | 348.70±36.87** | 11.13±1.63 | |
第28天 Day 28 | 对照组 Control group | 51.15±7.70 | 44.66±2.64 | 256.21±39.02 | 11.33±0.84 |
模型组 Model group | 84.76±18.18*** | 40.92±3.41 | 303.89±33.40* | 12.20±0.55 |
图3 末次免疫不同时间节点的对照组与模型组大鼠乳腺组织HE染色及CD138免疫组织化学染色结果(×400)
Figure 3 HE and CD138 staining results of mammary tissue in the control group and the model group at different time points after the final immunization (×400)
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