摘要
目的钙化性纳米微粒(CNPs)与泌尿系结石形成的关系已成为研究的热点,但其致肾结石形成的具体机制尚未明确。文中旨在对CNPs致肾结石形成机制进行研究。方法将48只大鼠随机分为CNPs组(每只大鼠经尾静脉注射2mL CNPs,建立CNPs的大鼠肾结石模型)、对照组(注射等量的无菌等渗盐水),每组24只。比较2组3 h、6 h、12 h、24 h、1周、2周、4周、8周时间点肾组织中自噬相关蛋白Beclin-1、LC-3蛋白的相对表达量、自噬体的形成和钙盐晶体形成情况。结果CNPs组3 h、6 h、12 h、24 h、1周、2周、4周、8周Beclin-1、LC-3蛋白的相对表达量及阳性细胞数较对照组明显增高(P<0.05),24 h达到最高值(P<0.05)。CNPs组24 h、1周、2周、4周、8周自噬体数量[(2.83±0.32)、(3.00±0.26)、(3.70±0.44)、(3.90±0.98)、(4.70±0.51)个/HP]较对照组[(0.73±0.15)个/HP]明显增加(P<0.05)。CNPs组2周、4周、8周钙盐晶体评分较对照组显著增加(P<0.05)。钙盐晶体的形成评分[(0.92±0.98)分]与Beclin-1、LC-3的表达强度[(6.78±4.25)、(2.61±2.57)]呈正相关(r=0.843、0.628,P<0.05),和自噬体数量[(2.53±1.41)个]呈正相关(r=0.923,P<0.001)。结论CNPs可能会损伤肾小管上皮细胞,诱导细胞即刻自噬活动,自噬相关蛋白表达及自噬体形成增加,在一定程度上促进肾小管中钙盐晶体的形成和聚集。
Objective The relationship between calcified nanoparticles(CNPs)and the formation of urinary stones is drawing increasing attention and the specific mechanisms involved.This study aims to investigate the mechanisms of the formation of kidney stone caused by CNPs.Methods A total of 48 rats were randomly and equally divided into a CNPs group(each rat was injected with 2 mL CNPs through the tail vein to establish a rat kidney stone model of CNPs),and a control group(injected the same amount of sterile isotonic saline instead of CNPs).We compared the expression levels of autophagy-related proteins,such as Beclin-1 and LC-3,the formation of autophagosomes and calcium salt crystals in renal tissues at time points of 3h,6h,12h,24h,1w,2w,4w and 8w in two groups.Results The relative expression levels and positive cells of Beclin-1 and LC-3 in CNPs group at 3h,6h,12h,24h,1w,2w,4w,8w were significantly higher than those in the control group(P<0.05),and reached the highest value at 24(P<0.05).The number of autophagosomes at 24h,1w,2w,4w,and 8w in the CNPs group((2.83±0.32),(3.00±0.26),(3.70±0.44),(3.90±0.98),(4.70±0.51)/HP,respectively)were significantly higher than those in the control group(0.73±0.15)/HP(P<0.05).The scores of calcium salt crystals in the CNPs group at 2w,4w,and 8w significantly increased compared to the control group(P<0.05).The calcium salt crystal formation score((0.92±0.98)points)was positively correlated with the expression intensities of Beclin-1 and LC-3((6.78±4.25),(2.61±2.57),respectively)(r=0.843,0.628,P<0.05),which was positively correlated with the number of autophagosomes(2.53±1.41)(r=0.923,P<0.001).Conclusion CNPs may damage renal tubular epithelial cells,and induce immediate autophagic activity,also increase expression of autophagy-related proteins and autophagosome formation,which will promote the formation and aggregation of calcium salt crystals in renal tubules to some extent.
作者
刘鑫
陈洁
朱永生
戢美英
陈春梅
陈开发
粟宏伟
LIU Xin;CHEN Jie;ZHU Yong-sheng;JI Mei-ying;CHEN Chun-mei;CHEN Kai-fa;SU Hong-wei(Department of Urology,Affiliated Hospital of Traditional Chinese Medicine,Southwest Medical University,Luzhou 646000,Sichuan,China;Graduate School,Southwest Medical University,Luzhou 646000,Sichuan,China)
出处
《医学研究生学报》
CAS
北大核心
2020年第1期44-49,共6页
Journal of Medical Postgraduates
基金
四川省科技厅科研项目（14JC0105）
西南医科大学科研项目（2017-ZRQN-082）
关键词
钙化性纳米微粒
肾结石
自噬
自噬相关蛋白
自噬体
calcified nanoparticles
kidney stone
autophagy
autophagy-related proteins
autophagosomes
