| Ischemia-reperfusion injury is one of the main causes of acute kidney injury(AKI).In many preclinical studies,the pathological changes of the renal cortex and the medullary are often used for diagnosis.These factors make it difficult to achieve AKI.Early diagnosis,prevention and treatment.The transient receptor potential melastain 2(TRPM2)channel is a recently discovered non-glutamate-dependent ion channel that has been shown to be widely expressed in brain and heart cells.Under ischemic injury,TRPM2 channels can be activated and mediate calcium transport,causing intracellular calcium overload.Studies at home and abroad show that TRPM2 plays an important role in mediating ischemic renal injury and oxidative stress,but its role in the process of ischemia-reperfusion AKI and its possible mechanism of action are still unclear.Here we conducted the following experiment.Objectives:To investigate the role of TRPM2 pathway in acute renal injury induced by ischemia-reperfusion and to explore its possible mechanism.Methods:SD rats were established by ischemia-reperfusion acute kidney injury model.SD rats were randomly divided into four groups:1.Sham group(sham group);2.Ischemia-reperfusion group(control group);Experiment A group;4.Experiment B group(8 in each group).After the AKI model was established in rats of experimental group A,TRPM2 agonist:ADPR(10mg/kg)was administered by intraperitoneal injection;In the experimental group B rats,after ischemic reperfusion AKI model was prepared,the TRPM2 inhibitor was given:AMP(5 mg/kg)was administered by intraperitoneal injection;the ischemic reperfusion group received intraperitoneal injection of the same dose of physiological fluid;the sham group received the same amount of saline injected intraperitoneally.Regular drug injections were performed after surgery,and the serum creatinine,urea nitrogen,and TGF-β1 expression levels were measured periodically in each group of rats,and the trend was plotted.On the 21st day of the experiment,each group of rats was sacrificed and the left kidney was collected for preparation.Paraffin sections,frozen sections,HE staining were used to observe the gross morphological changes,and immunofluorescence was used to detect TRPM2 expression in renal tissues.Results:1)Compared with the control group,TRPM2 agonist and inhibitor intervention factors had no significant difference in renal tissue fibrosis(renal tubular and interstitial structural changes),renal atrophy(P>0.05);2)After comparing the changes of serum creatinine and urea nitrogen in four groups of rats,it is concluded that inhibition of TRPM2 pathway has a positive effect on the recovery of renal function in AKI rats;activation of TRPM2 pathway is not conducive to the recovery of renal function in AKI rats The difference was statistically significant(P<0.05);3)The immunohistochemical staining of frozen sections of kidneys in group A,group B,control and sham was performed.There were no obvious abnormalities in renal tubules and glomeruli in the sham group,and TRPM2 was not expressed.In the experimental group A,TRPM2 was found in the renal tubules.The interstitial location was significantly clustered and expressed,and the integrity of renal tubular morphology was lower than that of the control group.The expression of experimental group B was close to that of the control group,and there was no significant difference in the integrity of renal tubules between the control group and the control group.4)By comparing the sham group,the control group,the experiment group A,and the experiment group B,it is concluded that there is no statistical difference in the expression of TGF-β1 after each group of rats.Conclusion:TRPM2 is involved in the process of ischemia-reperfusion.Early inhibition of TRPM2 can effectively improve the AKI caused by ischemia-reperfusion. |
PDF Full Text Request