Departments of Endocrinology, Chongqing General Hospital, University of Chinese Academy of Sciences, Departments of EndocrinologyChongqing General HospitalUniversity of Chinese Academy of SciencesChinaChina.
Departments of Emergency, Chongqing General Hospital, University of Chinese Academy of Sciences, Departments of EmergencyChongqing General HospitalUniversity of Chinese Academy of SciencesChinaChina.
Clinics (Sao Paulo). 2021 Jan 22;76:e2096. doi: 10.6061/clinics/2021/e2096. eCollection 2021.
To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy.
Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35).
At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group.
RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.
探讨甲状腺素功能减退症（简称甲减）孕鼠子代肾组织中 RBP4/PiC/SIRT3 信号通路在开放线粒体通透性转换孔（mPTP）中的作用。
将 60 只 Sprague-Dawley（SD）大鼠用于本研究。当在子宫内发现精子时，认为妊娠成功。妊娠 1 周后，将子代大鼠分为以下几组：全部甲减组（OH 组）、亚临床甲减组（SCH 组）和正常对照组（CON 组）。当血清促甲状腺激素（TSH）水平高于正常值且 TT4 水平在正常范围内时，即可确认甲减模型的建立。在第 14 天（P14）和第 35 天（P35）时提取子代大鼠的肾线粒体。
在 P14 时，与 SCH 组相比，OH 组大鼠 mPTP 开放程度和磷酸载体（PiC）的表达无明显差异，但沉默交配型信息调节 3 同源物（SIRT3）的表达水平显著降低。与 SCH 组相比，OH 组大鼠视黄醇结合蛋白 4（RBP4）的表达增加。在 P35 时，OH 组大鼠 mPTP 开放程度以及 PiC 和 RBP4 的表达水平均高于 SCH 组，而 OH 组 SIRT3 的表达水平低于 SCH 组。
RBP4 在甲减孕鼠子代早期肾线粒体损伤和肾功能损害中起重要作用。因此，RBP4/PiC/SIRT3 通路参与了子代大鼠甲亢时肾 mPTP 的开放。
