OBJECTIVE: The objective of this study was to examine the effectiveness of LBP in preventing lead-induced renal injury and investigate both the toxic mechanism of lead-induced renal injury and the efficacy mechanism of LBP against it, with a focus on the PI3K/AKT/mTOR signaling pathway.
METHODS: The drug effect and mechanism of LBP on lead-induced kidney injury were investigated by administering positive drugs and LBP to mice with established lead-induced kidney injury.
RESULTS: The renal function of mice with lead-induced renal injury was significantly restored, renal tissue lesions and renal mitochondrial damage were delayed, a disorder of hematological parameters induced by lead was improved, the increase of lead-induced renal index was reduced, and the body weight of mice with lead-induced renal injury was increased by the LBP intervention, as revealed by the results of pharmacodynamic experiments. Based on PI3K /AKT /mTOR signaling pathway, the toxic mechanism of lead-induced kidney injury and the pharmacodynamic mechanism of LBP against lead-induced kidney injury were studied. The results showed that lead could activate the TLR4 receptor, and then activate PI3K /AKT /mTOR signaling pathway, inhibit autophagy of kidney tissue cells, and enhance apoptosis of kidney tissue cells to induce kidney injury; LBP inhibits the activation of TLR4 receptor, which in turn inhibits the PI3K/AKT/mTOR signaling pathway, enhances the autophagy of kidney tissue cells, reduces the apoptosis of kidney tissues, and delays lead-induced kidney injury.
目的:本研究的目的是研究LBP预防铅肾损伤的有效性,并探讨铅肾损伤的毒性机制和LBP的疗效机制。重点关注PI3K/AKT/mTOR信号通路。
方法:通过对已建立的铅肾损伤小鼠给予阳性药物和LBP,研究LBP对铅肾损伤的作用和机制。
结果:铅致肾损伤小鼠的肾功能显著恢复,肾组织损伤和肾线粒体损伤延迟,铅引起的血液学参数紊乱得到改善,铅诱导肾指数的增加减少,LBP干预可增加铅肾损伤小鼠的体重,正如药效学实验的结果所揭示的那样。基于PI3K/AKT/mTOR信号通路,研究了铅肾损伤的毒性机制和LBP抗铅肾损伤的药效学机制。结果表明,铅可以激活TLR4受体,然后激活PI3K/AKT/mTOR信号通路,抑制肾组织细胞自噬,促进肾组织细胞凋亡,诱导肾损伤;LBP抑制TLR4受体激活,进而抑制PI3K/AKT/mTOR信号通路,增强肾组织细胞的自噬,减少肾组织的凋亡,并延缓铅引起的肾损伤。