Ahmadi Fatemeh, Amohashemi Elahe, Kazemi Mohammad, Salehi Hossein, Reisi Parham
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2025 Jun 17;20(3):343-355. doi: 10.4103/RPS.RPS_46_24. eCollection 2025 Jun.
The Klotho () gene, an aging suppressor in rats, accelerates aging when disrupted and extends lifespan when overexpressed. It encodes a transmembrane protein primarily expressed in renal tubules. This study investigated the protective effects of central Klo, both alone and in combination with cholinergic anti-inflammatory pathway (CAP) inhibition, against ischemia-reperfusion injury (IRI)- induced acute kidney injury. The current study evaluated the expression of inflammatory and anti-inflammatory genes (including and ) in the kidney, alongside plasma levels of creatinine (Cr), blood urea nitrogen (BUN), and signs of acute tubular injury.
Klo was microinjected into the rostral ventrolateral medulla, and CAP inhibition was achieved through intraperitoneal administration of mecamylamine (Mec). Real-time RT-PCR and hematoxylin and eosin staining were used for gene expression analysis and histopathological examination, respectively.
FINDINGS/RESULTS: The results showed elevated Cr and BUN levels, tubular injury, and increased inflammatory gene expression in IRI and IRI + Mec groups, as well as reduced in the IRI + Mec group. Klo exhibited protective effects. Elevated expression was seen in IRI + Klo and IRI + Mec + Klo groups one week post-surgery.
These findings indicated Klo potential to extend lifespan and protect against age-related diseases, including kidney disease and inflammation, neural modulation of peripheral immunity.
Klotho（）基因是大鼠中的一种衰老抑制因子，基因破坏时会加速衰老，过表达时则可延长寿命。它编码一种主要在肾小管中表达的跨膜蛋白。本研究调查了中枢Klotho单独以及与胆碱能抗炎通路（CAP）抑制联合使用时，对缺血再灌注损伤（IRI）诱导的急性肾损伤的保护作用。本研究评估了肾脏中炎症和抗炎基因（包括 和 ）的表达，以及血浆肌酐（Cr）、血尿素氮（BUN）水平和急性肾小管损伤的迹象。
将Klotho显微注射到延髓头端腹外侧，通过腹腔注射美加明（Mec）实现CAP抑制。分别使用实时RT-PCR和苏木精-伊红染色进行基因表达分析和组织病理学检查。
结果显示，IRI组和IRI + Mec组的Cr和BUN水平升高、肾小管损伤以及炎症基因表达增加，而IRI + Mec组的 降低。Klotho表现出保护作用。术后一周，IRI + Klotho组和IRI + Mec + Klotho组的 表达升高。
这些发现表明Klotho具有延长寿命和预防包括肾脏疾病和炎症在内的与年龄相关疾病的潜力，以及对外周免疫的神经调节作用。
