Effect of Slit3 on kidney fibrosis in diabetic kidney disease rats

Abstract

ObjectiveTo explore the effect of slit guidance ligand 3 （Slit3） on rats with diabetic kidney disease （DKD）-induced fibrosis.MethodsA DKD rat model was established by multiple low-dose injections of streptozotocin combined with high-sugar high-fat diet. Forty Sprague-Dawley （SD） rats were randomly divided into the blank control group （control）， diabetes mellitus （DM） group， 4-week DKD group and 8-week DKD group， with 10 rats in each group by random number table method. After successful modeling， there were 8 rats in the control group， and 6 in each of the remaining groups. The 24 h urinary protein content was detected. Total cholesterol （TC）， triglyceride （TG）， blood urea nitrogen （BUN）， serum creatinine （Scr）， and albumin （Alb） were analyzed after abdominal aorta blood collection. Hematoxylin and eosin （H&E） staining was used to observe the histopathological changes of the kidney. Kidney fibrosis degree was examined by Masson’s trichrome staining. The reverse-transcription quantitative real-time polymerase chain reaction （RT-qPCR） was performed to detect mRNA levels of Slit3， α-smooth muscle actin （α-SMA）， and transforming growth factor-β1 （TGF-β1） in kidney tissues， and their protein levels were detected by Western blot. The expression and localization of Slit3 in kidney tissues were detected by immunohistochemical staining.ResultsCompared with the control group， 24-hour urinary protein content ［（37.18 ± 5.55）mg、（47.38 ± 18.19）mg vs （10.66 ± 4.87）mg］， BUN ［（19.18 ± 7.97）mmol/L、（21.01 ± 6.74）mmol/L vs （6.86 ± 1.15）mmol/L］ and Scr ［（58.02 ± 12.49）μmol/L、（61.18 ± 20.76）μmol/L vs （28.34 ± 3.35）μmol/L］ of 4-week and 8-week DKD groups were significantly higher （P0.05）.ConclusionSlit3 can significantly aggravate kidney fibrosis in DKD rats.

Keywords

• slit guidance ligand 3
• diabetic kidney disease
• kidney fibrosis