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α-胎蛋白在糖皮质激素诱导的大鼠结肠早熟成熟过程中的作用。

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon.

机构信息

Lian Yun Gang Higher Vocational Technical College of Traditional Chinese Medicine, Lianyungang 222006, Jiangsu Province, China.

出版信息

World J Gastroenterol. 2011 Jun 28;17(24):2933-40. doi: 10.3748/wjg.v17.i24.2933.

Abstract

AIM

To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon.

METHODS

Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP.

RESULTS

Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon.

CONCLUSION

GCs promote the development of rat colon. AFP appears to be involved, in part, in mediating the effects of GCs in the developmental colon.

摘要

目的

研究甲胎蛋白(AFP)在糖皮质激素诱导的大鼠结肠早熟成熟中的作用,甲胎蛋白是一种与癌症相关的胎儿糖蛋白。

方法

本研究采用哺乳期 Sprague-Dawley 大鼠的结肠。出生后第 7、9 和 11 天,给正常幼崽注射 100μg/g 体重的醋酸考的松诱导高皮质醇血症。对照动物注射等体积的生理盐水。一些在出生后 7 天接受考的松的大鼠也用米非司酮(RU38486)治疗,一种糖皮质激素细胞质受体拮抗剂,以研究糖皮质激素(GCs)的作用。通过反转录聚合酶链反应和 Western 印迹检测结肠中 AFP 的表达水平。为了鉴定 AFP 在发育中的大鼠结肠中的细胞定位,使用针对特定间充质细胞标记物和 AFP 的抗体进行双免疫荧光染色。

结果

与对照组相比,皮质酮增加了 8 天和 10 天龄高皮质醇血症大鼠结肠的隐窝深度和绒毛高度(绒毛高度增加 120%,8 天龄大鼠和 118%,10 天龄大鼠,P=0.021;隐窝深度增加 145%,8 天龄大鼠和 124%,10 天龄大鼠,P=0.017)。这些增加伴随着 mRNA 和蛋白质中 AFP 表达的增加(8 天龄大鼠增加 2.5 倍,10 天龄大鼠增加 2.5 倍,高于对照组,P=0.035;8 天龄大鼠增加 1.8 倍,10 天龄大鼠增加 1.3 倍,高于对照组,P=0.023)。高皮质醇血症大鼠结肠中隐窝深度和绒毛高度的增加以及 AFP 的表达被米非司酮阻断。两者对 AFP 或波形蛋白均有阳性染色,在每个测试的结肠中的间充质细胞中均重叠。

结论

GC 促进大鼠结肠的发育。AFP 似乎部分参与了 GCs 在发育中的结肠中的作用。

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