背景:急性肾损伤(AKI)的特征是肾脏快速下降。牙周炎,慢性口腔炎性疾病,日益与肾功能障碍有关。虽然牙周炎被认为是肾脏损害的一个因素,与AKI相关的机制尚不清楚.
方法:本研究探讨了牙龈卟啉单胞菌(P.牙龈)W83感染的牙周炎对C57BL/6J小鼠的AKI,使用缺血再灌注损伤感染后55天。牙龈疼痛抑制剂,应用KYT-1和KYT-36。牙龈卟啉单胞菌的检测使用定量实时聚合酶链反应(qRT-PCR)和PCR,而转录组测序,qRT-PCR,免疫组织化学,和免疫荧光染色评估肾损伤。体外,HK-2细胞以10的感染复数暴露于牙龈卟啉单胞菌48小时,被牙龈蛋白酶或制瘤素M(OSM)抑制。使用qRT-PCR对紧密连接(TJ)的破坏进行定量,跨上皮电阻,和细胞计数试剂盒-8测定。
结果:牙周炎加重了AKI,与牙龈卟啉单胞菌感染和肾脏TJ破坏有关。牙龈卟啉单胞菌感染激活OSM表达,与牙龈痛呈正相关。重要的是,OSM和牙龈痛可能共同导致肾脏TJ的损伤,与TJ蛋白的表达降低。抑制牙龈疼痛活性是一种保护策略,可以防止TJ的破坏以及随之而来的牙周炎引起的AKI恶化。
结论:我们的研究增强了对牙周炎和AKI之间相互作用的理解,强调牙龈卟啉单胞菌在AKI中的有害影响。
BACKGROUND: Acute kidney injury (AKI) is characterized by rapid renal decline. Periodontitis, a chronic oral inflammatory disease, is increasingly associated with renal dysfunction. Although periodontitis is recognized as a contributor to kidney damage, the mechanisms linking it to AKI remain unclear.
METHODS: This study explored the effects of Porphyromonas gingivalis (P. gingivalis) W83-infected periodontitis on AKI in C57BL/6J mice, using ischemia-reperfusion injury 55 days post-infection. Gingipain inhibitors, KYT-1 and KYT-36, were applied. Detection of P. gingivalis was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and PCR, while transcriptome sequencing, qRT-PCR, immunohistochemistry, and immunofluorescence staining assessed renal damage. In vitro, HK-2 cells were exposed to P. gingivalis at a multiplicity of infection of 10 for 48 h, with inhibition by gingipain or oncostatin M (OSM). Disruption of tight junctions (TJs) was quantified using qRT-PCR, transepithelial electrical resistance, and cell counting kit-8 assays.
RESULTS: Periodontitis worsened AKI, linked to P. gingivalis infection and renal TJ disruption in the kidney. P. gingivalis infection activated OSM expression, which correlated positively with gingipain. Significantly, OSM and gingipain might collaboratively contribute to the damage of renal TJs, with the reduced expression of TJ proteins. Suppressing gingipain activity presented itself as a protective strategy against the destruction of TJs and the attendant worsening of AKI due to periodontitis.
CONCLUSIONS: Our study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of P. gingivalis in AKI.