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狼毒对大鼠膀胱肿瘤模型中微血管密度及癌细胞凋亡的影响。

Effects of Stellera chamaejasme on microvascular density and apoptosis of cancer cells in a rat bladder tumor model.

作者信息

Huang Yudong, Zhang Jun, Zhang Baolin, Chen Shuang, Qiang Ziyang, Ren Hailin, Chen Guojun, Ren Chengde

机构信息

Department of Urology, Qinghai University Affiliated Hospital, Xining, China.

出版信息

Transl Androl Urol. 2022 Mar;11(3):293-303. doi: 10.21037/tau-22-32.

DOI:10.21037/tau-22-32
PMID:35402196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8984973/
Abstract

BACKGROUND

Investigate the effects of Stellera chamaejasme on microvascular density and apoptosis of cancer cells in rat bladder tumor models.

METHODS

The bladder tumor model of 75 specific pathogen-free (SPF)-grade Sprague-Dawley (SD) rats aged 5-6 weeks was established by n-methyl-N-nitrosourea (MNU) bladder perfusion induction, and the model rats were randomly divided into model group, low-dose (L-dose) group, medium-dose (M-dose) group, high-dose (H-dose) group, and positive drug (hydroxycamptothecine, HCPT) group. L-dose group, M-dose group, and H-dose group were treated with 5 g/kg, 10 g/kg, and 20 g/kg, respectively. The HCPT group was treated with 2 mg/kg hydroxycamptothecin at 1 mL/kg once a week and the model group were treated with the same amount of normal saline for 4 weeks. The quality of bladder cancer tissues in each group was measured. The pathological changes and microvascular density of bladder tissues were observed, and the apoptosis rate of vascular endothelial growth factor (VEGF), tumor tissue and the protein expression levels of factor associated suicide (Fas), factor associated suicide ligand (FasL) and Caspase3 in bladder tissues were detected.

RESULTS

Bladder cancer was induced 14 weeks after initial bladder perfusion with MNU. In the model group, epithelial cells of bladder tissue showed atypically hyperplasia with various sizes and disorders. After treatment with Stellera chamaejasme, the hematoxylin-eosin (HE) scores, bladder weight, microvascular density, and VEGF were significantly decreased, and the tumor inhibition rate, cell apoptosis, and the expression of apoptosis-related proteins Fas, FasL, and Caspase3 were significantly increased in the bladder tissue. The above changes were dose-dependent with Stellera chamaejasme.

CONCLUSIONS

MNU can be used to prepare a rat bladder cancer model. Stellera chamaejasme has a good therapeutic effect on rat bladder cancer, which may inhibit the progression of bladder cancer by inhibiting micro-angiogenesis and inducing the apoptosis of bladder tumor cells.

摘要

背景

研究瑞香狼毒对大鼠膀胱肿瘤模型中微血管密度及癌细胞凋亡的影响。

方法

采用N-甲基-N-亚硝基脲(MNU)膀胱灌注诱导法建立75只5-6周龄无特定病原体(SPF)级Sprague-Dawley(SD)大鼠膀胱肿瘤模型,将模型大鼠随机分为模型组、低剂量(L-剂量)组、中剂量(M-剂量)组、高剂量(H-剂量)组和阳性药物(羟基喜树碱,HCPT)组。L-剂量组、M-剂量组和H-剂量组分别给予5 g/kg、10 g/kg和20 g/kg。HCPT组每周1次给予2 mg/kg羟基喜树碱,剂量为1 mL/kg,模型组给予等量生理盐水,连续给药4周。测量各组膀胱癌组织质量。观察膀胱组织的病理变化及微血管密度,检测血管内皮生长因子(VEGF)、肿瘤组织的凋亡率以及膀胱组织中相关自杀因子(Fas)、相关自杀配体(FasL)和半胱天冬酶3(Caspase3)的蛋白表达水平。

结果

首次膀胱灌注MNU后14周诱发膀胱癌。模型组膀胱组织上皮细胞出现大小不一、排列紊乱的非典型增生。经瑞香狼毒治疗后,膀胱组织苏木精-伊红(HE)评分、膀胱重量、微血管密度及VEGF均显著降低,肿瘤抑制率、细胞凋亡率以及凋亡相关蛋白Fas、FasL和Caspase3的表达均显著升高。上述变化与瑞香狼毒呈剂量依赖性。

结论

MNU可用于制备大鼠膀胱癌模型。瑞香狼毒对大鼠膀胱癌具有良好的治疗效果,其可能通过抑制微血管生成和诱导膀胱肿瘤细胞凋亡来抑制膀胱癌的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/0b053b549b86/tau-11-03-293-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/0da2c6b8e7db/tau-11-03-293-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/982f3ff8468f/tau-11-03-293-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/754bfd8f7b36/tau-11-03-293-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/f66e89c92996/tau-11-03-293-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/319c07003e04/tau-11-03-293-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/0335c03ec1c6/tau-11-03-293-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/0b053b549b86/tau-11-03-293-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/0da2c6b8e7db/tau-11-03-293-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/982f3ff8468f/tau-11-03-293-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/754bfd8f7b36/tau-11-03-293-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/f66e89c92996/tau-11-03-293-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/319c07003e04/tau-11-03-293-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/0335c03ec1c6/tau-11-03-293-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467a/8984973/0b053b549b86/tau-11-03-293-f7.jpg

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