急性顺铂治疗后大鼠小肠中促胰液素、胆囊收缩素和生长抑素的免疫组织化学定位

Immunohistochemical localizations of secretin, cholecystokinin, and somatostatin in the rat small intestine after acute cisplatin treatment.

作者信息

Miyamoto Yohei, Miyamoto Mari

机构信息

Toxicology Laboratory, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa 248-8555, Japan.

出版信息

Exp Mol Pathol. 2004 Dec;77(3):238-45. doi: 10.1016/j.yexmp.2004.05.007.

DOI:10.1016/j.yexmp.2004.05.007

PMID:15507242

Abstract

Cisplatin (CDDP) is an antitumor platinum complex that causes the well-studied side effect of renal tubular failure. In the present study, the acute effects of CDDP treatment on the localization of gut hormones in the rat small intestine were examined by immunohistochemistry. Male Sprague-Dawley rats were used for these experiments. Rats were injected intravenously with CDDP (3 mg/kg) in saline or were left untreated (control). After the rats were euthanized at 1, 3, 5, or 10 days after CDDP treatment, the small intestines (duodenum, jejunum, and ileum) were quickly removed, fixed, embedded in paraffin, and cut. No mucosal toxicity was detected by histopathological observation in any of the intestines of CDDP-treated rats. The immunohistochemical detection was performed using anti-secretin, anti-cholecystokinin (CCK), and anti-somatostatin with the avidin-biotin-immuno-peroxidase procedure. The total number of immunoreactive cells per complete cross-section was counted. In the duodenum, the numbers of secretin-immunoreactive cells and somatostatin-immunoreactive cells were dramatically increased 5 days after CDDP treatment. In the jejunum, the number of CCK-immunoreactive cells was increased 1 day after CDDP treatment and those of secretin-immunoreactive cells and CCK-immunoreactive cells were increased 5 days after CDDP treatment. In the ileum, the number of CCK-immunoreactive cells was increased 1 day after CDDP treatment. The change in the secretin-immunoreactive cell count may be caused by metabolic inhibition of gastrin following CDDP-induced nephrotoxicity. The change in the CCK-immunoreactive cell count may promote the excretion of bile. Therefore, somatostatin may regulate secretin and CCK secretion. We conclude that the distribution of these hormone-immunoreactive cells in the rat small intestine might be controlled by CDDP-induced nephrotoxicity without gut mucosal toxicity.

摘要

顺铂（CDDP）是一种抗肿瘤铂类复合物，会导致已被充分研究的肾小管衰竭副作用。在本研究中，通过免疫组织化学检查了CDDP处理对大鼠小肠中肠道激素定位的急性影响。雄性Sprague-Dawley大鼠用于这些实验。大鼠静脉注射生理盐水溶解的CDDP（3mg/kg）或不进行处理（对照）。在CDDP处理后1、3、5或10天对大鼠实施安乐死后，迅速取出小肠（十二指肠、空肠和回肠），固定、石蜡包埋并切片。在接受CDDP处理的大鼠的任何肠道中，组织病理学观察均未检测到黏膜毒性。使用抗促胰液素、抗胆囊收缩素（CCK）和抗生长抑素，通过抗生物素蛋白-生物素免疫过氧化物酶法进行免疫组织化学检测。对每个完整横截面中免疫反应性细胞的总数进行计数。在十二指肠中，促胰液素免疫反应性细胞和生长抑素免疫反应性细胞的数量在CDDP处理后5天显著增加。在空肠中，CCK免疫反应性细胞的数量在CDDP处理后1天增加，促胰液素免疫反应性细胞和CCK免疫反应性细胞的数量在CDDP处理后5天增加。在回肠中，CCK免疫反应性细胞的数量在CDDP处理后1天增加。促胰液素免疫反应性细胞计数的变化可能是由CDDP诱导的肾毒性后胃泌素的代谢抑制引起的。CCK免疫反应性细胞计数的变化可能会促进胆汁的排泄。因此，生长抑素可能调节促胰液素和CCK的分泌。我们得出结论，大鼠小肠中这些激素免疫反应性细胞的分布可能受CDDP诱导的肾毒性控制，而无肠道黏膜毒性。