非手术子宫注射法建立大鼠盆腔炎模型的研究
作者单位:

吉林医药学院

基金项目:

吉林省科技厅重点攻关项目(20240305074YY);吉林省发展和改革委员会产业技术研究与开发项目(2023C027-8);山东省中医药科技项目(Z-2023065);吉林医药学院研究生创新计划项目(2023yyc02)


Study on the establishment of rat model of pelvic inflammatory disease by non-surgical uterine injection
Author:
Affiliation:

Jilin Medical University

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    摘要:

    【摘要】 目的 非手术法建立高效、稳定的大鼠盆腔炎模型,并评估验证其在药效试验中的应用。方法 雌性SD大鼠随机分为对照组、苯酚7天模型组、苯酚10天模型组、苯酚造模治疗组、低浓度菌液模型组、高浓度菌液模型组和菌液造模治疗组。模型组和治疗组SD大鼠以非手术法子宫腔注射25%苯酚凝胶、2×107个或2×108个大肠埃希菌和金黄色葡萄链球菌的混合菌,以构建盆腔炎模型。治疗组大鼠灌胃复方中药-清盆活血汤,对照组大鼠在相同时间给予等体积的溶剂溶液。观察大鼠的健康状况、体重变化和子宫外观;计算子宫系数;HE染色检测子宫和输卵管的病理变化、子宫内膜厚度和腺体数量;ELISA检测大鼠血清中IL-1β、IL-6和TNF-α水平;免疫荧光染色检测巨噬细胞标志物CD68蛋白表达;western blotting检测大鼠子宫中TLR4/NF-KB通路相关蛋白表达。 结果 模型组大鼠的死亡率只有5%;与对照组相比,造模后大鼠体重下降、子宫系数增加、子宫和输卵管出现不同程度的病理变化、内膜变薄、腺体数量减少、血清IL-1β、IL-6、TNF-α的水平和子宫组织中巨噬细胞的数量显著增加、TLR4/NF-kB信号通路被激活;苯酚7天模型和低浓度菌液模型被判定为轻度盆腔炎模型,苯酚10天模型和高浓度菌液模型被判定为重度盆腔炎模型;中成药金刚藤治疗后,子宫和输卵管的病理症状明显缓解,符合临床盆腔炎的药效评估。结论 通过非手术法利用苯酚和混合菌液建立的大鼠盆腔炎模型可以更好地模拟临床由于不同原因导致的不同程度病理状态的盆腔炎,适用于药物药效作用评价和盆腔炎病理机制的阐明。

    Abstract:

    【Abstract】 Objective To establish an efficient and stable model of pelvic inflammatory disease in rats by non-surgical method and evaluate its application in pharmacodynamic test. Methods Female SD rats were randomly divided into control group, model group treated with phenol for 7 days, model group treated with phenol for 10 days, Chinese medicine treatment group with phenol modeling, model group with low concentration of bacterials, model group with high concentration of bacterias and Chinese medicine treatment group with bacterial modeling. SD rats in model group or treatment group were injected with 25% phenol gel, 2×107 or 2×108 Escherichia coli and Staphylostreptococcus aureus mixture by non-surgical method to construct the rat model of pelvic inflammatory disease. The rats in the treatment group were gavaged with Qingpen Huoxue decoction, and the rats in the control group were given the same volume of solvent solution at the same time. The health status, weight change and uterine appearance of rats were observed. The uterine coefficient was calculated. HE staining was used to detect pathological changes of uterus and fallopian tube, endometrial thickness and number of glands. Serum levels of IL-1β, IL-6 and TNF-α were detected by ELISA. Macrophage marker CD68 protein expression was detected by immunofluorescence staining. The expression of TLR4/NF-KB pathway-related proteins in the uterus of rats was detected by western blotting. Results The mortality rate in the model group was only 5%. Compared with the control group, the body weight of rats decreased, uterine coefficient increased, pathological changes of uterus and fallopian tube appeared in different degrees, endometrium thinned, the number of glands decreased, serum levels of IL-1β, IL-6, TNF-α and the number of macrophages in uterine tissue increased significantly, and TLR4/NF-kB signaling pathway was activated. The 7-day phenol model and low-concentration bacterial solution model were judged to be mild pelvic inflammatory disease model, and the 10-day phenol model and high-concentration bacterial solution model were judged to be severe pelvic inflammatory disease model. After the treatment of Chinese patent medicine--Jingangteng, the pathological symptoms of uterus and fallopian tube were obviously relieved, which was in line with the efficacy evaluation of clinical pelvic inflammatory disease. Conclusion The rat model of pelvic inflammatory disease established by using phenol and mixed bacterial solution in non-surgical method can better simulate the different pathological states of pelvic inflammatory disease caused by different causes, which is suitable for drug efficacy evaluation and elucidating the pathological mechanism of pelvic inflammatory disease.

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  • 收稿日期:2024-06-27
  • 最后修改日期:2024-09-05
  • 录用日期:2025-02-19
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