摘要
背景:胰岛素样生长因子1(IGF 1)是一种功能强大的神经保护分子。我们以前已经证明短期下丘脑IGF 1基因治疗能恢复老年雌性大鼠的结核性漏斗多巴胺能神经元功能。目的:对老年雌性大鼠垂体泌乳素瘤进行IGF-I基因治疗。方法:观察IGF 1基因治疗对携带自发性垂体泌乳素瘤的幼龄(4mo.)和老年(24 Mo)雌性大鼠下丘脑的长期疗效。我们构建并注射了一个表达大鼠IGF 1基因或报告红色荧光蛋白DsRed基因的帮助依赖型(HD)腺样体。注射载体后91天,处死所有大鼠,并固定其大脑和垂体。用放射免疫法测定血清催乳素(PRL)、雌二醇(E2)、孕酮(P4)及下丘脑IGF 1含量。用抗大鼠PRL抗体免疫垂体前叶,并进行形态计量学分析。结果:DsRed组大鼠下丘脑中叶部DsRed表达较强,而IGF 1组中IGF 1含量较高。IGF 1对幼年大鼠垂体重量及PRL、E2、P4水平均无影响。在老年大鼠中,IGF 1基因治疗可使大鼠腺体重量较正常大鼠减少,PRL水平较正常大鼠明显降低。治疗显着地挽救了老年腺瘤中泌乳细胞群的表型。结论:长期应用下丘脑IGF 1基因治疗老年雌性大鼠自发性泌乳素瘤是有效的。
关键词: 衰老,下丘脑,垂体,腺瘤,PRL,IGF-1,基因治疗。
Current Gene Therapy
Title:IGF-1 Gene Therapy as a Potentially Useful Therapy for Spontaneous Prolactinomas in Senile Rats
Volume: 18 Issue: 4
关键词: 衰老,下丘脑,垂体,腺瘤,PRL,IGF-1,基因治疗。
摘要: Background: Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibular dopaminergic neuron function in aging female rats.
Objective: Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile female rats.
Methods: Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young (4 mo.) and aging (24 mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed and injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or the reporter red fluorescent protein DsRed. Ninety-one days post vector injection, all rats were sacrificed and their brains and pituitaries fixed. Serum prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as hypothalamic IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with an anti-rat PRL antibody and submitted to morphometric analysis.
Results: DsRed expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The IGF1 treatment affected neither pituitary weight nor PRL, E2 or P4 serum levels in the young rats. In the old rats, IGF1 gene therapy reduced gland weight as compared with intact counterparts and tended to reduce PRL levels as compared with intact counterparts. The treatment significantly rescued the phenotype of the lactotropic cell population in the senile adenomas.
Conclusion: We conclude that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous prolactinomas in aging female rats.
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Cite this article as:
IGF-1 Gene Therapy as a Potentially Useful Therapy for Spontaneous Prolactinomas in Senile Rats, Current Gene Therapy 2018; 18 (4) . https://dx.doi.org/10.2174/1566523218666180905170020
DOI https://dx.doi.org/10.2174/1566523218666180905170020 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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