Effects Of Cannabinoid Receptor 2 Agonist On Acute Renal Injury In Septic Rats

Objective:To investigate the effect and mechanism of cannabinoid receptor 2agonist on acute renal injury in septic rats.Method: Twenty-four healthy adult male SD rats were divided into three groups(n = 8)according to the random number table :sham operation group(Sham group),sepsis group(Sep group)and sepsis + CB2 R Agonist JWH133 group(Sep + JWH133group).The cecal ligation and puncture method was used to establish a sepsis rat model.The Sep + JWH133 group was intraperitoneally injected with JWH133 1.5 mg/ kg within 15 minutes after surgery.The Sham group and the Sep group were given the same amount of saline at the same time.After 24 h of modeling,the heart was bled.ELISA to detect serum creatinine(SCr)levels;HE staining light microscope to observe pathological changes in the kidney tissue;immunohistochemical method to determine the expression levels of autophagy-related proteins Beclin-1,Atg5;Transmission electron microscope(TEM)was used to observe the damage of mitochondria in the proximal tubule epithelial cells of the kidney..Results: Under light microscope,the Sham group was normal small intestine and kidney,no bleeding and inflammatory infiltration,and the injury degree of small intestinal tissue < 1.In Sep group,the intestinal villous epithelium was absent or interrupted,mucosal vascular hemorrhage,a large number of inflammatory cells infiltrated,the degree of tissue injury ≥ 3,the arrangement of renal proximal tubular epithelial cells was disordered,the glomerular volume was significantly enlarged,Mesangial cells were swollen,and there were obvious hemorrhage and a large number of inflammatory cell infiltration in the interstitium.In Sep+JWH133 group,the pathological changes were alleviated obviously,the villous epithelial tissue of small intestine was intact,there was only a little vascular bleeding,a small amount of inflammatory cell infiltration,and the degree of tissue injury was less than grade 2;the structure of kidney was intact,and there was only a small amount of hemorrhage and inflammatory cell infiltration in interstitium.Compared with the Sham group,the SCr value and the renal tubular Paller’s score of the Sep group and the Sep + JWH133 group were significantly increased(P <0.05);the expression of Beclin-1 and Atg5 was up-regulated(P<0.05);more mitochondrial damage was observed in renal proximal tubular epithelial cells under the transmission electron microscope(TEM)(P < 0.05).Compared with the Sep group,the SCr value and renal tubular Paller’s score of the Sep + JWH133 group decreased(P <0.05);the expression level of Beclin-1 and Atg5 was increased(P<0.05);the degree of mitochondrial damage was reduced as shown by TEM(P<0.05).Conclusion: The CB-R2 agonist attenuated AKI in septic rats,probably by up-regulating the expression of renal autophagy and reducing the degree of mitochondrial damage.