| Objective: To investigate the protective effects of Curcumin on rat with diabetic nephropathy as well as the functional mechanism.Methods:The rats were divided into control group,DN model group and treatment groups randomly.The 24 h before the rats were killed with metabolic cages to collect 24 h urine,and then the next day were sacrificed blood and kidney tissue.Serum and urine were also collected for BG and BUN and Scr and urinary protein testing;renal tissue pathological changes were detected by HE staining;each group rats of SOD and MDA were detected;real-time quantitative PCR to detect the expression of each group of Nrf2 and HO-1gene mRNA;Nrf2 protein expression by immuno-histochemistry;HK-2 cells were cultured in vitro and the content of SOD and MDA in cell culture supernatant was detected under different stimulation conditions.Nrf2 and HO-1 expression in different conditions were detected by Western blot and real-time quantitative PCR.Results: Biochemical indices of rats showed that BG,BUN,Scr and UACR in DN group were significantly higher than those in control group,and the difference was statistically significant;but after curcumin intervention,BG,BUN,Scr and UACR content decreased,and the difference was statistically significant.The results of HE staining showed that the glomerular structure of the control group was clear and the tubular morphology was regular;the glomerular structure of the DN group was unclear,and a large number of inflammatory cells infiltrated into the glomerulus,and the tubular cytoplasm was shallow,the cavity was large and vacuole-like;compared with the DN group,the kidney injury of the LC and HC groups were alleviated,the glomerulus was clearer,and the tubular edema was decreased.In HC group,renal injury was more obvious.Compared with the control group,the content of SOD decreased and the content of MDA increased in DN group,the difference was statistically significant(P<0.05);Compared with the DN group,the content of SOD increased and the content of MDA decreased in LC and HC groups,the HC group changed most significantly,the difference was statistically significant(P<0.05).Real-time quantitative PCR was used to detect the expression of Nrf2 mRNA.The results showed that compared with the control group,high glucose environment could promote the expression of Nrf2;Curcumin could further promote the expression of Nrf2 mRNA under high glucose stimulation,which was concentration-dependent,and the difference was statistically significant(P<0.05).Immunohistochemical staining showed that Nrf2 was expressed in kidney tissues of rats in each group;the expression of Nrf2 protein in DN group was significantly higher than that in control group;a large number of strongly positive brown granules were observed in HC group,significantly higher than that in DN group and LC group(P<0.05).By detecting the culture supernatant of HK-2 cells,the results showed that compared with the A group,SOD content of group B decreased,MDA content increased,the difference was statistically significant(P<0.05);compared with group B,SOD content of group C and group D increased,MDA content decreased,the indicators of group D were more obvious,the difference was statistically significant(P<0.05).Compared with the A group,the expression of Nrf2 increased in B group,and further increased in a dose-dependent manner when high glucose and curcumin co-stimulated(P<0.05).The results of real-time quantitative PCR and Western blot showed that compared with the control group,the expression of HO-1 increased in a dose-dependent manner under Nrf2 activator stimulation and the difference was statistically significant(P<0.05).Conclusion: Curcumin can delay kidney injury in rats with diabetic nephropathy by Nrf2/HO-1 signaling pathway. |
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