Abstract：
Triphenyltin (TPT) is a class of organotin compounds that are extensively used in industry and agriculture. They have endocrine-disrupting effects and cause severe environmental contamination. Pollutants may accumulate in the kidneys and cause pathological complications. However, the mechanism of TPT\'s toxicological effects on the kidney remains unclear. This study aimed to investigate the toxic effects and mechanism of action of TPT exposure on renal impairment in rats. Male SD rats were divided into four groups: the Ctrl group (control group), TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 28 days of exposure to TPT, we observed the morphology and structure of kidney tissue using HE, PASM, and Masson staining. We also detected serum biochemical indexes, performed transcriptome sequencing of rat kidney tissue using RNA-seq. Furthermore, protein expression levels were measured through immunohistochemistry and gene expression levels were determined using RT-qPCR. The study results indicated a decrease in kidney weight and relative kidney weight after 28 days of exposure to TPT. Additionally, TPT caused damage to kidney structure and function, as evidenced by HE staining, PASM staining, and serum biochemical tests. Transcriptomics identified 352 DEGs, and enrichment analyses revealed that TPT exposure primarily impacted the renin-angiotensin system (RAS). The expression levels of water channel proteins were reduced, and the expression levels of RAS and lipid metabolism-related genes (Mme, Ace, Fasn, Cyp4a8, Cpt1b and Ppard) were significantly decreased in the TPT-treated group. In summary, exposure to TPT may impair renal structure and function in rats by affecting RAS, AQPs, and lipid metabolism.
摘要：
三苯基锡(TPT)是一类广泛用于工业和农业的有机锡化合物。它们具有内分泌干扰作用并引起严重的环境污染。污染物可能在肾脏中积聚并引起病理并发症。然而,TPT对肾脏的毒理作用机制尚不清楚。本研究旨在探讨TPT暴露对大鼠肾损害的毒性作用及其作用机制。雄性SD大鼠分为四组:Ctrl组(对照组),TPT-L组（0.5mg/kg/d），TPT-M组（1mg/kg/d），和TPT-H组（2mg/kg/d）。TPT暴露28天后，我们用HE观察肾脏组织的形态和结构，PASM,和Masson染色。我们还检测了血清生化指标，使用RNA-seq对大鼠肾组织进行转录组测序。此外，通过免疫组织化学测量蛋白质表达水平，并使用RT-qPCR确定基因表达水平。研究结果表明，暴露于TPT28天后，肾脏重量和相对肾脏重量降低。此外,TPT对肾脏结构和功能造成损害，如HE染色所证明，PASM染色,和血清生化测试.转录组学确定了352个DEG，和富集分析表明，TPT暴露主要影响肾素-血管紧张素系统（RAS）。水通道蛋白的表达水平降低，以及RAS和脂质代谢相关基因的表达水平(MME，Ace,Fasn,TPT治疗组的Cyp4a8，Cpt1b和Ppard）显着降低。总之,暴露于TPT可能通过影响RAS损害大鼠的肾脏结构和功能，AQPs,和脂质代谢。
