目的探讨心脏死亡供体器官捐献(donation after cardiac death,DCD)来源角膜植片行穿透性角膜移植后角膜内皮细胞变异情况.方法用角膜内皮显微镜对心脏死亡供体来源角膜植片行穿透性角膜移植191例眼术后角膜植片分别于术后1~4周;5~12周;...目的探讨心脏死亡供体器官捐献(donation after cardiac death,DCD)来源角膜植片行穿透性角膜移植后角膜内皮细胞变异情况.方法用角膜内皮显微镜对心脏死亡供体来源角膜植片行穿透性角膜移植191例眼术后角膜植片分别于术后1~4周;5~12周;4~6月;7~12月行角膜内皮镜检查.结果 (1)191例患者中有48例患者角膜内皮镜检出,143例患者角膜内皮镜无法检出,检出率占25%;(2)48例患者术后1~4周、2~3月、4~6月及7~12月的内皮细胞细胞密度(2271.15±321.47)个/mm^2、(1971.33±358.18)个/mm^2、(1826.59±303.92)个/mm^2、及(1753.14±306.31)个/mm^2.平均细胞面积由术前的(388.45±95.26)μm增加到术后7~12月的(638.63±124.73),细胞大小变异系数(cv值)由30.15%增加到65.04%,六角形细胞比例由(52.59±7.26)%下降到(40.01±11.35)%.结论 (1)角膜内皮镜检查对于早期角膜移植术后患者内皮细胞识别率较低,敏感度差,角膜移植术后早期内皮镜无法测出结果时可选择共焦显微镜评价观察角膜内皮细胞的变化;(2)穿透性角膜移植术后供眼角膜内皮细胞密度逐渐减少,六角形细胞比例渐变小平均细胞面积和cv值均渐增大.(3)DCD角膜移植术后1 a,尤其是术后3月应加强术后随访,当发现有早期排斥反应的征象时,及时进行抗排斥治疗对于减少早期排斥反应尤为重要.展开更多
目的:探讨心脏死亡供体器官捐献(donation after cardiac death,DCD)来源角膜植片术后排斥反应与角膜内皮细胞的相关性。方法:用角膜内皮显微镜对心脏死亡供体来源角膜植片行穿透性角膜移植术后发生排斥反应的28例28眼角膜植片分别于术...目的:探讨心脏死亡供体器官捐献(donation after cardiac death,DCD)来源角膜植片术后排斥反应与角膜内皮细胞的相关性。方法:用角膜内皮显微镜对心脏死亡供体来源角膜植片行穿透性角膜移植术后发生排斥反应的28例28眼角膜植片分别于术后<1、2~3、4~6、7~12mo行角膜内皮镜检查。结果:28例患者术后<1、2~3、4~6、7~12mo的角膜内皮细胞变异系数分别为38.23%、49.56%、57.18%、65.04%;角膜内皮细胞密度分别为2071.15±311.47、1771.33±348.18、1626.59±353.92、1553.14±307.31个/mm2;角膜内皮细胞变异系数与排斥反应呈正相关关系(r=0.95,P<0.05);术后角膜内皮细胞密度与排斥反应呈负相关关系(r=-0.93,P<0.05)。结论:DCD穿透性角膜移植术后发生排斥反应时有角膜内皮细胞变异系数逐步增高,角膜内皮细胞密度逐步降低的趋势;角膜内皮细胞变异系数、角膜内皮细胞密度可作为早期检测术后排斥反应的指标。展开更多
Effective clearance of oxidized, damaged, and/or misfolded proteins in the cell by the ubiquitin-proteasome system (UPS) is critical for cell homeostasis, survival and function. We hypothesized that in the aging heart...Effective clearance of oxidized, damaged, and/or misfolded proteins in the cell by the ubiquitin-proteasome system (UPS) is critical for cell homeostasis, survival and function. We hypothesized that in the aging heart, generation of free radicals could impair UPS where the associated build-up of polyubiquitinated proteins could trigger programmed cell death. To test this, we used young (4 months old) and aged (24 months old) rats to analyze polyubiquitinated proteins, proteasome activity and programmed cell death in the ventricular tissue samples. Our studies reveal excessive deposition of polyubiquitinated proteins in the ventricular tissue extracts of old rats when compared to younger rats. The increased ubiquitination was accompanied by a significant decrease in 20S proteasome activity. Since the loss of proteasome-mediated clearance of ubiquitinated proteins is linked to programmed cell death, we measured TUNEL activity in aged rat heart and compared with younger animals. Aged animal hearts showed a substantial increase in programmed cell death as evidenced by TUNEL positive nuclei and DNA fragmentation. Analyses of cell death/survival pathways support our findings in terms of age-associated increase in the nuclear localization of p53, Bax/Bcl2 ratio and cleaved (active) caspase-3 and decreased expression of cellular inhibitor of apoptosis (cIAP1). Administration of grape seed extract (GSE) as a source of antioxidants significantly reduced these age-associated deleterious changes suggesting that free radicals primarily contribute to impaired UPS function and increased programmed cell death and that administration of antioxidants during aging could protect cardiac muscle cells and preserve ventricular function.展开更多
基金This work was supported by research grants from American Diabetes Association (07-02-JF-1007-05-CD-02), Philip Morris USA, Inc.(02-187) and Jewish Hospital ResearchFoundation (2001071508)
文摘目的:探讨心脏死亡供体器官捐献(donation after cardiac death,DCD)来源角膜植片术后排斥反应与角膜内皮细胞的相关性。方法:用角膜内皮显微镜对心脏死亡供体来源角膜植片行穿透性角膜移植术后发生排斥反应的28例28眼角膜植片分别于术后<1、2~3、4~6、7~12mo行角膜内皮镜检查。结果:28例患者术后<1、2~3、4~6、7~12mo的角膜内皮细胞变异系数分别为38.23%、49.56%、57.18%、65.04%;角膜内皮细胞密度分别为2071.15±311.47、1771.33±348.18、1626.59±353.92、1553.14±307.31个/mm2;角膜内皮细胞变异系数与排斥反应呈正相关关系(r=0.95,P<0.05);术后角膜内皮细胞密度与排斥反应呈负相关关系(r=-0.93,P<0.05)。结论:DCD穿透性角膜移植术后发生排斥反应时有角膜内皮细胞变异系数逐步增高,角膜内皮细胞密度逐步降低的趋势;角膜内皮细胞变异系数、角膜内皮细胞密度可作为早期检测术后排斥反应的指标。
文摘Effective clearance of oxidized, damaged, and/or misfolded proteins in the cell by the ubiquitin-proteasome system (UPS) is critical for cell homeostasis, survival and function. We hypothesized that in the aging heart, generation of free radicals could impair UPS where the associated build-up of polyubiquitinated proteins could trigger programmed cell death. To test this, we used young (4 months old) and aged (24 months old) rats to analyze polyubiquitinated proteins, proteasome activity and programmed cell death in the ventricular tissue samples. Our studies reveal excessive deposition of polyubiquitinated proteins in the ventricular tissue extracts of old rats when compared to younger rats. The increased ubiquitination was accompanied by a significant decrease in 20S proteasome activity. Since the loss of proteasome-mediated clearance of ubiquitinated proteins is linked to programmed cell death, we measured TUNEL activity in aged rat heart and compared with younger animals. Aged animal hearts showed a substantial increase in programmed cell death as evidenced by TUNEL positive nuclei and DNA fragmentation. Analyses of cell death/survival pathways support our findings in terms of age-associated increase in the nuclear localization of p53, Bax/Bcl2 ratio and cleaved (active) caspase-3 and decreased expression of cellular inhibitor of apoptosis (cIAP1). Administration of grape seed extract (GSE) as a source of antioxidants significantly reduced these age-associated deleterious changes suggesting that free radicals primarily contribute to impaired UPS function and increased programmed cell death and that administration of antioxidants during aging could protect cardiac muscle cells and preserve ventricular function.
