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在小鼠肺化学致癌过程中,V 型胶原减少与细胞凋亡的关系:一种研究癌细胞行为的初步模型。

Association between decreases in type V collagen and apoptosis in mouse lung chemical carcinogenesis: a preliminary model to study cancer cell behavior.

机构信息

Departament of Pathology, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil.

出版信息

Clinics (Sao Paulo). 2010 Apr;65(4):425-32. doi: 10.1590/S1807-59322010000400012.

Abstract

OBJECTIVE

The importance of type V collagen and its relationships with other types of collagen and with vascular and epithelial apoptosis were studied in a model of chemical carcinogenesis in the mouse lung.

METHODS

TWO GROUPS OF MALE BALB/C MICE WERE STUDIED: a) animals that received two intraperitoneal doses of 3 g/kg urethane carcinogen (urethane group = 24); and b) animals submitted to a sham procedure, comparable to the test group (control group = 7). Both groups were sacrificed after 120 days. In situ detection of apoptosis, immunohistochemistry, immunofluorescence and histomorphometry were used to evaluate the fraction occupied by the tumor, vascular and epithelial apoptosis, and type V, III and I collagen fibers in the lung parenchyma from both groups.

RESULTS

The lung parenchyma from the urethane group showed low fractions of vascular and epithelial apoptosis as well as reduced type V collagen fibers when compared to the control group. A significant direct association was found between type V and III collagen fibers and epithelial apoptosis, type V collagen fibers and vascular apoptosis, and type V and type I collagen fibers.

CONCLUSION

The results show that a direct link between low amounts of type V collagen and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis, suggesting that strategies aimed at preventing decreased type V collagen synthesis or local responses to reduced apoptosis may have a greater impact in lung cancer control.

摘要

目的

本研究旨在探讨化学致癌作用小鼠肺部模型中 V 型胶原及其与其他类型胶原以及血管和上皮细胞凋亡的关系。

方法

本研究共纳入两组雄性 BALB/c 小鼠:a)接受两次腹腔内 3 g/kg 乌氨酸致癌剂注射的动物(乌氨酸组=24 只);b)接受假手术处理、与试验组具有可比性的动物(对照组=7 只)。两组均于 120 天后处死。采用原位检测细胞凋亡、免疫组化、免疫荧光和组织形态计量学方法,评估两组小鼠肺实质中肿瘤、血管和上皮细胞凋亡以及 V、III 和 I 型胶原纤维的比例。

结果

与对照组相比,乌氨酸组小鼠肺实质中的血管和上皮细胞凋亡比例较低,V 型胶原纤维也较少。V 型和 III 型胶原纤维与上皮细胞凋亡、V 型胶原纤维与血管凋亡、V 型和 I 型胶原纤维之间均存在显著的直接相关性。

结论

这些结果表明,V 型胶原含量低与细胞凋亡减少之间可能存在直接联系,这可能有利于化学致癌作用后小鼠肺部癌细胞的生长。提示预防 V 型胶原合成减少或局部对凋亡减少的反应的策略可能会对肺癌的控制产生更大的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/657a/2862677/6a2222485060/cln_65p425f1.jpg

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