| Background:Kidney belongs to hyper-transfusion organ,and is very sensitive to ischemia or hypoxia.Renal ischemia reperfusion(I/R) injury can lead to acute tubular necrosis or acute renal insufficiency.At present,the studies show that pathophysiological mechanism of renal I/ R is extremely complex and is related to various factors,of which inflammatory response is important factor.The generation and distribution of inflammatory mediators have close connection with the activation of complement system.Angiotensin-converting enzyme inhibitors,such as captopril,are commonly used to treat renal I/R injury. Through the expansion of blood vessels,the blood flow is thus restored as soon as possible to reduce the ischemic time and prevent renal I/R injury.Objective:To investigate the mechanism of renal I/R injury and its key factors,and analyze how angiotensin-converting enzyme inhibitor (captopril) have a protective effect on renal I/R injury. Methods:In this study,I/R model was made through ligating one side renal vessel.Renal function indexes including Scr and BUN were detected through biochemical analysis;renal tissue and the corresponding protein expression were observed by pathomorphology and immunohistochemistry.At the same time,ELISA detection was used to determined inflammatory cytokines IL-6 and TNF-αin renal tissue and serum.IL-1β,TNF-αexpression and activation of MAPK signaling pathway were analyzed by RT-PCR and Western blot respectively. Turbidimetry was applied to essay serum complement.Results:After I/R for 1 h,Scr and BUN value started to increase, and presented significantly after 2 h.Inflammatory cell infiltration was found in renal glomeruli during reperfusion for 1 h after ischemia for 30 min;while 30 min of ischemia followed by 2 h of reperfusion, deterioration of renal tubular damage with cell necrosis was observed, and a large number of inflammatory cells was infiltrated in renal interstitium.However,the levels of inflammatory cytokines IL-6 and TNF-αin serum had no significant difference between sham group and I/ R groups for different times.The contents of IL-6 and TNF-αin renal tissue treated with I/R injury for 1 h or 2 h significantly increased compared with sham group.While reperfusion for 1 h after ischemia for 30 min,the mRNA levels of inflammatory cytokines IL-6,TNF-αwere obviously up-regulated. Western blot showed that when the renal ischemia for 30 min and without reperfusion,p38,ERK,JNK in MAPK signaling pathway were activated.With the extending of reperfusion time,p38,ERK and JNK were phosphorylated significantly(activated).At 30 min of reperfusion, MAPK phosphorylation was increased significantly,but then had no obvious change with the time of reperfusion.In addition,we found that BUN and Scr values were decreased markedly after treatment of renal I/R injury with captopril(angiotensin inhibitors),inflammatory cell infiltration in renal glomeruli was significantly reduced,and swelling of tubular epithelial cells on the proximal and juxtamedullary regions was decreased.At the same time, the level of inflammatory cytokines IL-6 in renal tissue was reduced. However,after treatment with captopril,the JNK,ERK and P38 phosphorylation in renal tissue was still high,which had no significant difference with I/R group.The serum complement activity(CH50) was significantly reduced during renal I/R injury,while recovered obviously after treatment with captopril.Immunocytochemistry revealed that 30 min of ischemia followed by 1 h of reperfusion,the depositions of complement activation fragment C3d were found at the basilar part of tubular epithelial cells on the proximal and juxtamedullary regions,which in amount or degree were degraded when treated with captopril.Western blot analysis indicated that activation fragment of complement C3(C3d) was observed in renal tissue after I/R injury(I/R group),and decreased after captopril treatment (CAP group).Conclusion:Renal I/R injury can lead to increased expression of pro-inflammatory cytokines in the tissues,and can activate MAPK signaling pathway.Captopril affects the activation of complement system rather than MAPK inflammatory signaling pathway,and thus lessens I/R injury of renal tissue through inhibiting expression of some inflammatory cytokines.
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