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雌二醇治疗和/或卵巢切除术对Sprague-Dawley大鼠胰岛自发性出血性病变的影响。

Effects of estradiol treatment and/or ovariectomy on spontaneous hemorrhagic lesions in the pancreatic islets of Sprague-Dawley rats.

作者信息

Imaoka Masako, Kato Michiyuki, Tago Satoko, Gotoh Mayumi, Satoh Hiroshi, Manabe Sunao

机构信息

Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13 Kita-Kasai, Edogawa-ku, Tokyo, Japan.

出版信息

Toxicol Pathol. 2009 Feb;37(2):218-26. doi: 10.1177/0192623308329283.

Abstract

The present study was conducted to investigate the effect of estradiol treatment and/or ovariectomy (OVX) on non-neoplastic lesions in the pancreatic islets of Sprague-Dawley rats. Males were divided into non-treatment (naïve) and beta-estradiol 3-benzoate (EB) treatment groups and females into naïve, sham-operation, OVX, and OVX plus EB treatment groups. EB was subcutaneously administered once a week from seven to twenty-six weeks of age. The animals were euthanized at twelve, eighteen, and twenty-six weeks of age, and the serum estradiol concentrations were measured in conjunction with the pancreatic islet histopathology. The histological stages of pancreatic findings were classified into three groups, hemorrhagic, fibrotic, and inflammatory lesions, and the incidence of each type of lesion was enumerated. In males, both the total and individual incidence of pancreatic lesions increased age dependently in the naïve group. EB treatment significantly decreased the total incidence at twenty-six weeks. This alteration consisted of fibrotic and inflammatory lesions, but not hemorrhagic lesions. Additionally, the incidence of hemorrhagic lesions was at the same level between male naïve and male EB groups at twelve weeks, despite a markedly higher concentration of serum estradiol in the EB group. In females, a similar tendency was seen, and the total incidence was generally low in the naïve group, whereas it was increased by OVX. OVX plus EB treatment tended to decrease the incidence accompanied by a marked increase in estradiol concentrations. In conclusion, estrogen was shown to inhibit the development of pancreatic islet lesions toward inflammation and fibrosis but did not inhibit the occurrence of hemorrhagic lesions.

摘要

本研究旨在探讨雌二醇治疗和/或卵巢切除术(OVX)对Sprague-Dawley大鼠胰岛非肿瘤性病变的影响。雄性大鼠分为未治疗(单纯)组和苯甲酸雌二醇(EB)治疗组,雌性大鼠分为单纯组、假手术组、OVX组和OVX+EB治疗组。从7周龄至26周龄,每周皮下注射一次EB。在12周、18周和26周龄时对动物实施安乐死,并结合胰岛组织病理学测量血清雌二醇浓度。胰腺病变的组织学阶段分为三组,即出血性、纤维化和炎症性病变,并统计每种病变类型的发生率。在雄性大鼠中,单纯组胰腺病变的总发生率和个体发生率均随年龄增长而增加。EB治疗在26周时显著降低了总发生率。这种变化包括纤维化和炎症性病变,但不包括出血性病变。此外,尽管EB组血清雌二醇浓度明显较高,但12周时雄性单纯组和雄性EB组的出血性病变发生率处于同一水平。在雌性大鼠中也观察到类似趋势,单纯组的总发生率通常较低,而OVX使其增加。OVX+EB治疗倾向于降低发生率,同时雌二醇浓度显著升高。总之,雌激素可抑制胰岛病变向炎症和纤维化发展,但不能抑制出血性病变的发生。

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