| Objective:To observe the effect of all-trans retinoic acid(ATRA)on renal ischemia-reperfusion injury(IRI)in rats,and explore its mechanism from the perspective of Nrf2/HO-1signaling pathway.Methods:A total of 24 healthy adult male SD rats were randomly divided into 3 groups,Sham operation group(Sham),renal ischemia/reperfusion(I/R)group,and all-trans retinoic acid(I/R+ATRA)group,with 8 rats in each group.The rats in Sham and I/R groups were given intraperitoneal injection of corn oil(1ml/kg/d)for 1 week.The rats in the ATRA group were injected intraperitoneally with ATRA dissolved in corn oil(10mg/kg/d)for 1 week.3groups of rats were anesthetized with 10% chloral hydrate(0.3ml/100g)and fixed limbs.And the left renal artery was separated from the abdominal cavity along the midabdominal line at 37℃.In the Sham group,the right kidney was excised without blocking the left renal artery.Renal I/R model was established by right nephrectomy combined with left renal artery occlusion for 45 min followed by 24 h reperfusion in I/R and ATRA groups.After the experiment,we collect three groups of rats serum and kidney tissue samples.The concentrations of serum creatinine(Scr)and blood urea nitrogen(BUN)were detected by colorimetric method.HE staining was used to observe the pathological changes of kidney tissue.The apoptosis of renal tissue cells was detected by TUNEL staining.The expression level of reactive oxygen species(ROS)in renal tissue was evaluated by dihydroethidium(DHE)fluorescence staining.A colorimetric method was used to determine the contents of superoxide dismutase(SOD)and malondialdehyde(MDA)in the kidney tissue.The protein expression levels of Nrf2 and HO-1 were detected by Western blot.Results:(1)Renal function detection of rats in 3 groups: Scr and BUN levels of rats in I/R group were increased compared with Sham group(P<0.01).Compared with I/R group,Scr and BUN contents in I/R+ATRA group were significantly increased(P<0.01),and the differences were statistically significant.(2)Renal histopathological examination,renal tubule injury score and apoptotic cell level detection in the 3 groups: Compared with Sham group,the pathological injury of rats in I/R group was more serious,the renal tubule injury score(3.13±0.64)was higher(P<0.05),and the expression of apoptotic cells was increased.Compared with the I/R group,the pathological changes of the I/R+ATRA group were significantly aggravated,the renal tubular injury score(4.88±0.35)was significantly higher(P<0.05),and the expression of apoptotic cells was significantly increased,the differences were statistically significant.(3)Detection of oxidative stress level of rats in 3 groups: Compared with Sham group,the relative expression of ROS and MDA content in kidney tissue were increased,and the activity of SOD was decreased in I/R group(P<0.05).Compared with the I/R group,the relative expression of ROS and MDA content in renal tissue after ATRA pretreatment were significantly increased,and the activity of SOD was significantly decreased(P<0.05),and the differences were statistically significant.(4)Expression levels of Nrf2 and HO-1 in rats in the 3 groups: Compared with Sham group,the protein expressions of Nrf2 and HO-1 in kidney tissue of rats in I/R group were increased(P<0.01).The protein levels of Nrf2 and HO-1 were lower in I/R+ATRA group than in I/R group(P<0.01),and the differences were statistically significant.Conclusion:(1)Nrf2/HO-1 signaling pathway is involved in the process of renal ischemia reperfusion.(2)ATRA may further aggravate renal I/R injury by inhibiting Nrf2/HO-1 pathway and aggravating oxidative stress. |
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