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猕猴发育过程中肠肝组织生长抑素及其受体表达演变规律

郭梅梅, 谭庆华, 范华, 黄明慧, 王春晖, 丘小庆, 唐承薇

四川大学华西医院国家生物治疗重点实验室人类疾病相关多肽研究室.四川，成都 610041

摘要

探讨在猕猴发育过程中生长抑素(somatostatin, SST)及其受体在肠肝组织的演变规律。通过手术途径获得胚胎6月、 新生2 d、新生45 d和成年猕猴的回肠、肝脏、门静脉和外周血等标本。应用放射免疫分析法测定各标本中的SST含量； 通过免疫组化方法观察SST在肠、肝组织内的分布；利用原位杂交检测SST受体2 (somatostatin receptor 2, SSTR2)的表达。结果显示：(1)胚胎6 月的猕猴，小肠内SST含量为(27.3±16.6) ng/mg蛋白；黏膜隐窝处SST呈弱阳性染色，肌层SST染色阴性。在发育过程中，小肠内SST含量逐渐增加，成年期时达最高水平(120.1±35.3) ng/mg蛋白，较胚胎6月显著增加(P<0.01)。 (2)成年小肠黏膜隐窝处及肌间神经丛SST呈强阳性染色。 (3)胚胎6月，小肠粘膜上皮可见大量SSTR2表达，成年时SSTR2表达下调，且主要定位于腺上皮隐窝处；胚胎及新生期肌层SSTR2染色阴性，成年时小肠肌间神经 丛则可见阳性SSTR2染色。 (4)肝脏在发育过程中SST及SSTR2含量逐渐降低；发育的各个时期，小肠组织的SST含量均 明显高于肝脏组织含量，门静脉SST水平也始终高于外周血。总之，位于小肠黏膜隐窝处的SST和SSTR2随着发育逐渐 增加，来自肠道的SST进入门静脉后迅速被降解。SST阳性的肠肌间神经丛仅在发育成熟后才出现。

关键词： 生长抑素; 生长抑素受体; 发育; 猕猴; 小肠; 肝脏

Changes of somatostatin and expression of somatostatin receptor in small intestine and liver tissues during macaque development

Guo Meimei, Tan Qinghua, Fan Hua, Huang Minghui, Wang Chunhui, Qiu Xiaoqing, Tang Chengwei

Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy of Human Diseases, West China Hospital, Sichuan University.Chengdu 610041,Sichuan

Abstract

Intestinal tract, which produces more than fifty kinds of gut peptides, is regarded as the largest endocrine organ. With regard to the gut peptides, a number of studies were focused on their structure, function and the roles in some diseases. The changes in output or distribution of gut peptides in the intestinal tract during development have been largely unknown. This study was aimed to investigate the changes of somatostatin (SST) and somatostatin receptor 2 (SSTR2) in small intestinal and hepatic tissues during the development of macaque. The tissue samples of small intestine, liver or blood samples from peripheral and portal vein of 4 macaques in 6-month fetus, 2-day neonate, 45-day neonate and adult were obtained after anesthetization. The concentrations of SST in blood or tissues of macaques were measured by radioimmunoassay. The distributions of SST in small intestinal or hepatic tissues were visualized by immunohistochemical staining. The expression of SSTR2 was detected by in situ hybridization. SST concentration of intestinal tissue in 6-month-old macaque was (27.3±16.6) ng /mg protein and light positive staining of SST was localized in mucosal crypts but negative in muscle layer. The intestinal concentration of SST increased gradually with macaque development and reached to the peak [(120.1±35.3) ng /mg protein] in adult. It was significantly higher than that in fetus (P<0.01). Strong positive staining of SST was found in both mucosal crypts and myenteric nerve plexus of adult animal. SSTR2 was obviously expressed in intestinal epithelium of fetus but its expression was greatly reduced in epithelium and was shifted to mucosal crypts when grown to adult. Negative staining of SSTR2 in muscle layer of fetal or neonatal macaque turned to be positive in myenteric nerve plexus of adult. The levels of SST or SSTR2 in liver decreased gradually during development. SST concentrations of small intestinal tissue kept significantly higher than those of hepatic tissues in the macaque developing stages. SST levels of portal vein were also maintained significantly higher than those of peripheral blood in the macaque developing stages. In conclusion, the level of SST and expression of SSTR2 in mucosal crypt increased gradually with macaque development. SST from intestinal tract was quickly degraded in portal vein before entering into liver. SST positive myenteric nerve plexus was visualized only in mature macaque.

Key words: Somatostatin;Somatostatin receptor;Development;Macaque;Small intestine;Liver

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引用本文：

郭梅梅, 谭庆华, 范华, 黄明慧, 王春晖, 丘小庆, 唐承薇. 猕猴发育过程中肠肝组织生长抑素及其受体表达演变规律[J]. 生理学报 2005; 57 (6): .

Guo Meimei, Tan Qinghua, Fan Hua, Huang Minghui, Wang Chunhui, Qiu Xiaoqing, Tang Chengwei. Changes of somatostatin and expression of somatostatin receptor in small intestine and liver tissues during macaque development . Acta Physiol Sin 2005; 57 (6): (in Chinese with English abstract).