Macula densa NOS1 and transplanted renal graft function
Macula densa NOS1 and transplanted renal graft function
批准号:
10380831
负责人:
Lei Wang
金额:
$32.89万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-04-16 至 2025-03-31
关键词:
BicarbonatesCardiac DeathConsciousDataDeteriorationEmploymentEnd stage renal failureExhibitsFeedbackGenerationsGlomerular Filtration RateGraft SurvivalHalf-LifeIn VitroIncidenceInjury to KidneyIntakeIschemiaKidneyKidney TransplantationLeadLifeMacula densaMeasurementMeasuresMediatingMethodsMusNOS1 geneNeuronsNitric Oxide SynthaseNitric Oxide Synthase Type IOrganOrgan DonorOrgan SurvivalOrgan TransplantationOutcomePatientsPlayPreventionPrevention strategyProceduresRNA SplicingRenal functionReperfusion InjuryRisk FactorsRoleSavingsSurvival RateTestingTransplant RecipientsTransplantationVariantWild Type Mousedelayed graft functionexperienceexperimental studygraft functionhemodynamicsimprovedin vitro activityin vivonovelnovel strategiespost-transplantresponsetherapeutic targettranslational potential
中文摘要
肾移植是终末期肾病患者的救命手段
疾病。尽管移植后的短期器官存活率有了显著改善
在过去的几十年里,长期的结果仍然不满意的生存半衰期
移植肾仍有10年左右的时间。此外,器官短缺是一场全球性的危机,
促进了利用边缘器官扩大捐赠库的新方法。
然而,使用边缘器官的患者延迟移植的发生率明显更高。
与标准供者相比,移植肾功能和移植物存活率较低。因此,有
迫切需要新的战略来改善移植的长期结果。
在这项提议中,一个新的假设是通过以下方式挽救致密斑NOS1的表达
用碳酸氢盐对肾脏进行碱化可改善移植肾的效果,将进行测试。
本提案的结论将提供一种有潜力的新战略。
肾移植期间可应用于供者或受者的翻译意义
移植。此外,还将研究潜在的机制和潜在的目标。
肾脏碱化增强供体或肾组织致密斑区NOS1的表达
预计接受者是一种简单而有效的方法,用于扩大
捐赠库和提高移植物的长期存活率。
英文摘要
Kidney transplantation is a life-saving procedure for patients with end-stage kidney
disease. Although the short-term organ survival post-transplantation has improved dramatically
over the past decades, the long-term outcomes remain unsatisfied with the survival half-lives for
transplanted renal grafts still about 10 years. In addition, organ shortage is a global crisis which
has stimulated new approaches on expansion of the donor pool by using marginal organs.
However, the employment of marginal organs has a significantly higher incidence of delayed graft
function and lower graft survival rate compared with standard criteria donors. Therefore, there is
an urgent need for new strategies to improve the long-term graft outcomes.
In this proposal, a novel hypothesis that rescue macula densa NOS1 expression by
renal alkalization with bicarbonate improves transplanted graft outcomes will be tested.
The findings of the present proposal will provide a novel strategy with potential
translational significance that could be applied to either donors or recipients during kidney
transplantation. Additionally, the underlying mechanisms and potential targets will be examined.
Renal alkalization to enhance the expression of macula densa NOS1 expression in donors or
recipients is anticipated to be a simple and effective method that is used in the expansion of the
donor pool and improvement of long-term graft survival.
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