器官移植2025，Vol.16Issue(3)：404-415,12.DOI:10.12464/j.issn.1674-7445.2025074
舒洛地特通过保护血管内皮糖萼减轻肾脏长时间缺血-再灌注损伤后肾纤维化
Sulodexide alleviates renal fibrosis following prolonged ischemia-reperfusion injury by protecting vascular endothelial glycocalyx
摘要
Abstract
Objective To investigate the protective effects and mechanisms of sulodexide on renal fibrosis induced by prolonged warm ischemia.Methods An in vivo ischemia-reperfusion injury(IRI)model was established in rats,which were randomly divided into Sham group,IRI 60 min group(IRI group),and IRI 60 min+sulodexide group(IRI+SDX group),with 20 rats in each group.Pathological examination was used to evaluate renal tissue injury and fibrosis levels in each group.Immunohistochemistry was performed to detect the expression levels of kidney injury molecule(KIM)-1,intercellular adhesion molecule(ICAM)-1,von Willebrand factor(vWF),transforming growth factor(TGF)-β,α-smooth muscle actin(SMA),and type I collagen(COL-1).Immunofluorescence staining was used to detect CD31 expression.Real-time quantitative polymerase chain reaction was employed to measure the expression of KIM-1,ICAM-1,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and IL-6 in renal tissues.Transmission electron microscopy was used to observe the structure of the renal glycocalyx.Evans blue dye was injected to assess renal vascular permeability.Rat survival was recorded,and serum levels of syndecan(SDC)-1,heparan sulfate(HS)and serum creatinine were measured.An ex vivo perfusion model was also established,with rats randomly assigned to either the hypothermic oxygenated machine perfusion(HOPE)group or the HOPE+SDX group(five rats per group).Perfusion parameters were recorded after 2 hours of ex vivo perfusion.Results One day after reperfusion,compared with the Sham group,the IRI group exhibited more severe renal tissue injury,higher tubular injury scores,increased expression of KIM-1,ICAM-1 and vWF,decreased CD31 expression,elevated serum levels of SDC-1 and HS,increased vascular permeability,and higher expression of TNF-α,IL-1β and IL-6.Compared with the IRI group,the IRI+SDX group showed reduced renal tissue injury,lower tubular injury scores,decreased expression of KIM-1,ICAM-1 and vWF,increased CD31 expression,lower serum levels of SDC-1 and HS,decreased vascular permeability,and reduced expression of TNF-α,IL-1β and IL-6(all P<0.05).Ten days after reperfusion,renal tissue injury was further alleviated in the IRI+SDX group.Twenty-five days after reperfusion,the IRI+SDX group exhibited decreased expression of TGF-β,α-SMA,and COL-1,as well as reduced collagen deposition area(all P<0.05).Compared with the HOPE group,the HOPE+SDX group showed increased renal perfusion flow and decreased intrarenal vascular resistance(both P<0.01).Conclusions Sulodexide may alleviates renal IRI and fibrosis caused by prolonged warm ischemia by inhibiting inflammatory responses and protecting vascular endothelial glycocalyx.关键词
舒洛地特/低温携氧机械灌注/肾移植/缺血-再灌注损伤/炎症反应/血管内皮/糖萼/纤维化Key words
Sulodexide/Hypothermic oxygenated machine perfusion/Kidney transplantation/Ischemia-reperfusion injury/Inflammation/Vascular endothelium/Glycocalyx/Fibrosis分类
医药卫生引用本文复制引用
胡超禹,张鹏,孙超,莫舒咏,王彦峰..舒洛地特通过保护血管内皮糖萼减轻肾脏长时间缺血-再灌注损伤后肾纤维化[J].器官移植,2025,16(3):404-415,12.基金项目
国家自然科学基金面上项目(82270793) （82270793）
深圳市基础研究专项(自然科学基金)基础研究面上项目(JCYJ20240813104159051) （自然科学基金）
