Rapamycin Alleviates Hormone Imbalance-Induced Chronic Nonbacterial Inflammation in Rat Prostate Through Activating Autophagy via the mTOR/ULK1/ATG13 Signaling Pathway
Rapamycin Alleviates Hormone Imbalance-Induced Chronic Nonbacterial Inflammation in Rat Prostate Through Activating Autophagy via the mTOR/ULK1/ATG13 Signaling Pathway
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DOI：
10.1007/s10753-018-0786-7
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发表时间：
2018-04
期刊：
影响因子：
5.1
通讯作者：
Yang Su;Jingxiao Lu;Xianguo Chen;C. Liang;Pengcheng Luo;Cong Qin;Jie Zhang
中科院分区：
文献类型：
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作者：
Yang Su;Jingxiao Lu;Xianguo Chen;C. Liang;Pengcheng Luo;Cong Qin;Jie Zhang
摘要慢性前列腺炎（CP）是临床上常见病，发病率高。由于下尿路和生殖器症状反复出现，严重影响患者的生活质量和身心健康。由于对CP病因的认识尚不统一，因此很难治疗甚至治愈。自噬是一种广泛存在于真核细胞中的高度保守的生理功能。一般来说，细胞在生理条件下维持一定水平的自噬，在饥饿、感染、创伤等应激情况下，自噬的基础水平可受多种自噬相关基因的调控。因此，本研究的主要目的是探讨自噬在慢性非细菌性前列腺炎（CNP，也称为CP）中的作用。本研究以去势大鼠为实验对象，皮下注射17β-雌二醇，然后腹腔注射雷帕霉素（一种常见的自噬诱导剂），建立CNP模型。然后分别检测大鼠前列腺组织、外周血单个核细胞（PBMCs）和血清中核因子-κB （NF-κB）、白细胞介素-1β (IL-1β)和自噬相关标志物的表达及自噬小体的形成。除了前列腺组织的一些组织学变化外，我们发现模型组NF-κB和IL-1β水平显著升高，自噬明显抑制，而雷帕霉素可以逆转这些作用，这些作用涉及mTOR/ULK1/ATG13信号通路。总之，我们的研究结果表明，雷帕霉素可以通过激活自噬来改善激素失衡引起的CNP。
AbstractChronic prostatitis (CP) is a clinically common disease with high morbidity. It affects the patients’ quality of life (QoL) as well as physical and mental health seriously due to the recurring symptoms of lower urinary tract and genitalia. As the opinions about the etiology of CP are still not uniform, it is very difficult to be treated or even cured. Autophagy is a highly conserved physiological function which is widely found in eukaryotic cells. In general, cells maintain a certain level of autophagy under physiological conditions, and the basal level of autophagy can be regulated by a variety of autophagy-related genes under stress such as hunger, infection, trauma, and other circumstances. Therefore, the main purpose of this study is to investigate the role of autophagy in chronic nonbacterial prostatitis (CNP, also called CP). In this paper, we established the CNP modelviahypodermic injection of 17β-estradiol and subsequently abdominal rapamycin (a common autophagy inducer) treatment based on castrated rats. Then, the expression of nuclear factor-κB (NF-κB), interleukin-1β (IL-1β), and autophagy-related markers as well as autophagosome formation in prostate tissues, peripheral blood mononuclear cells (PBMCs), and serum of rats were evaluated respectively. In addition to some histological changes in the prostate tissues, we found the levels of NF-κB and IL-1β were significantly increased in the model group, along with significantly suppressed autophagy, whereas rapamycin could reverse these effects which involved in the mTOR/ULK1/ATG13 signaling pathway. In conclusion, our results suggested that rapamycin could ameliorate hormone imbalance-induced CNP by activating autophagy.