NF-κB plays a key role in ischemia reperfusion injury (IRI). Systemic inhibition of NF-κB by various methods has been proven to ameliorate IRI. However, NF-κB is also responsible for tissue protection against IRI. Systemic NF-κB inhibition may not be the optimal way for preventing IRI because of its complex roles. T cells are essential in mediating IRI. NF-κB is an important molecule during T cell activation. It is not clear the effect of T cell–specific NF-κB inhibition on IRI. We aimed to study the effect of T cell–specific NF-κB inhibition on renal IRI in IκBαΔN-Tg mice. We also compared the different effects between T cell–specific and systemic NF-κB inhibition on IRI.
Renal IRI was induced by left renal pedicle clamping for 60 or 80 min in wild-type, ursolic acid–treated or IκBαΔN-Tg mice. Renal function, histologic examination and overall survival after lethal IRI was evaluated in each group.
Serum creatinine, BUN, and pathologic damage were all reduced in IκBαDN-Tg mice and ursolic acid–treated mice than those in the control group. All the above indexes were improved better in IκBαDN-Tg mice than those in ursolic acid–treated mice. The survival rate of IκBαDN-Tg mice was higher than that of ursolic acid–treated mice after lethal kidney ischemia reperfusion injury. Immunohistochemistry showed a significant reduced CD4+ T cells and neutrophil infiltration in IκBαDN-Tg mice.
T cell–specific NF-κB inhibition provides powerful protective effect against renal IRI.