摘要
目的探讨蛋白激酶Cβ(PKCβ)抑制剂是否通过调节巨噬细胞表型来缓解肾脏缺血再灌注损伤(RIRI)。方法RIRI组大鼠血管夹阻断左肾血供60 min,同时切除右肾。Inhibitor+RIRI组予以PKCβ抑制剂在手术前1 d口服,余下处理同RIRI组。Sham组大鼠开腹后再闭腹。术后24 h处死大鼠,采集血液和左侧肾脏样本。分析肾功能、组织形态以及肾小管损伤标志物KIM-1,肾乳头损伤指标RPA-1、巨噬细胞亚型标志物及炎性因子的表达水平。结果PAS染色显示RIRI组大鼠肾切片有明显肾小管损伤,经PKCβ抑制剂干预后Inhibitor+RIRI组炎性细胞浸润、肾小管损伤评分降低(P<0.05)。RIRI组Cr、BUN、KIM-1和RPA-1的表达水平显著高于Sham组及Inhibitor+RIRI组(P<0.05)。与RIRI组相比,经PKCβ抑制剂干预后Inhibitor+RIRI组Cr、BUN、KIM-1和RPA-1表达显著减少(P<0.05)。RIRI组大鼠肾组织中iNOS、IL-12及CD197的表达显著高于Sham组及Inhibitor+RIRI组(P<0.05);与RIRI组相比,经PKCβ抑制剂干预后Inhibitor+RIRI组i NOS、IL-12及CD197蛋白表达量显著减少(P<0.05);经PKCβ抑制剂干预后Inhibitor+RIRI组Dectin-1、ARG-1和CD163的蛋白表达量明显高于RIRI组及Sham组(P<0.05)。结论PKCβ抑制剂可减轻缺血再灌注后肾功能不全、肾小管损伤、肾小管和肾乳头损伤标志物的表达。PKCβ抑制剂抑制M1巨噬细胞并促进巨噬细胞向M2极化,减少促炎并增加抗炎因子的表达促进肾脏修复。
Objective To investigate whether PKCβinhibitor can alleviate RIRI by regulating macrophage phenotype.Methods Rats in the renal ischemia⁃reperfusion injury(RIRI)model group underwent right nephrec⁃tomy followed by a 60⁃minute clamping of the left renal pedicle.In the experimental group(Inhibitor+RIRI),PKCβinhibitors were administered orally one day prior to surgery.All rats were euthanized 24 hours post⁃surgery for the collection of blood and left kidney samples.Renal function,tissue morphology,and the expression levels of renal tubular injury marker KIM⁃1,renal papilla injury marker RPA⁃1,macrophage subtype markers,and inflammatory factors were evaluated.Results PKCβinhibitors alleviated renal ischemia⁃reperfusion injury in rats.PAS staining revealed marked tubular damage in kidney sections from the RIRI group,whereas kidney inflammatory cell infiltra⁃tion and renal tubular injury scores were significantly reduced in the Inhibitor+RIRI group following PKCβinhibitor treatment(all P<0.05).The expression levels of Cr,BUN,KIM⁃1,and RPA⁃1 were markedly elevated in the RIRI group compared to the Sham and Inhibitor+RIRI groups(all P<0.05).After PKCβinhibitor intervention,the expression levels of Cr,BUN,KIM⁃1,and RPA⁃1 were significantly decreased in the Inhibitor+RIRI group relative to the RIRI group(all P<0.05).Protein expression levels of iNOS,IL⁃2,and CD197 in the kidney tissue of the RIRI group were significantly higher than those in the Sham and Inhibitor+RIRI groups(all P<0.05).Compared with the RIRI group,the protein expression levels of iNOS,IL⁃12,and CD197 were significantly reduced in the Inhibitor+RIRI group following PKCβinhibitor intervention(all P<0.05).Additionally,the protein expression levels of Dectin⁃1,ARG⁃1,and CD163 were significantly higher in the Inhibitor+RIRI group than in the RIRI and Sham groups after PKCβinhibitor intervention(all P<0.05).Conclusions PKCβinhibitors can mitigate renal dysfunction,renal tubular injury,and the expression of injury markers in the renal tubules and renal papilla follow⁃ing ischemia⁃reperfusion.Additionally,PKCβinhibitors play a role in modulating macrophage subtypes by reducing M1 macrophages and promoting polarization to M2,which leads to a decrease in pro⁃inflammatory factors and an increase in anti⁃inflammatory factors,ultimately facilitating kidney repair.
作者
李春燕
肖婷
伍邦翠
陈永
田梅
LI Chunyan;XIAO Ting;WU Bangcui;CHEN Yong;TIAN Mei(Department of Nephrology and Rheumatology,Affiliated Hospital of Zunyi Medical University,Zunyi 563003,Guizhou,China;不详)
出处
《实用医学杂志》
北大核心
2025年第1期23-29,共7页
The Journal of Practical Medicine
基金
国家自然科学基金项目(编号:82460325,81160096)
遵义市科技计划项目(编号:遵市科合HZ字(2023)205号)。
