Protective effects of tacrolimus on podocytes in early diabetic nephropathy in rats.
The aim of the present study was to investigate the protective effect of tacrolimus on early podocyte damage in rats with diabetic nephropathy (DN). A total of 38 normal male Sprague‑Dawley rats were randomly divided into four groups: Normal control group (group N; n=8), DN group (n=10), tacrolimus (FK506) treatment group (group F; n=10), benazepril (Lotensin) treatment group (group L; n=10). The rats in groups DN, F and L were administered with streptozotocin (STZ; 60 mg/kg) by intraperitoneal injection to establish the diabetic rat model. After 4 weeks, the diabetic rat model was established, and rats in the different groups were administered intragrastically with the respective drugs. Blood glucose (BS), body weight (BW) and 24‑h urine protein were detected every 4 weeks, serum creatinine (SCr), blood urea nitrogen (BUN) and kidney weight/body weight (KW/BW) were measured at the end of the 8 weeks of drug treatment. Renal pathological changes were observed under a light microscope and electron microscope. Expression of nephrin, which is a podocyte‑specific marker, was detected using western blot analysis. The results showed that the levels of SCr, BUN, KW/BW and 24‑h urine protein in groups D, F and L were significantly higher, compared with those in group N (P<0.05). No significant differences were found between groups F and L for the above indicators, with the exception of BS. However, all indices were significantly lower, compared with those in group DN (P<0.05). Renal pathological expression was normal in group N under light microscopy. There were significant increases in the glomerular volume, proliferative mesangial cells, width of the mesangial area and thickness of the basement membrane in group DN, however, all the above pathological characteristics were reduced in groups F and L, compared with group DN (P<0.05). No significant difference was found between groups F and L. A widened glomerular basement membrane, and disorder, widening and fusion of podocyte processes were observed under the electron microscope in group DN, however, these were reduced in groups F and L, compared with group DN (P<0.05). The results of the western blot analysis showed that the expression of nephrin decreased by 60.1% in group DN, compared with group N, and significant recovery in the expression of nephrin was observed in groups F and L (P<0.05). Tacrolimus reduced urinary protein and slowed the progression of DN, partially by recovering the protein expression of nephrin in the renal tissue of diabetic rats, and maintaining the integrity of the structure and function of podocytes.
Department of Nephrology, Shandong University Qilu Hospital, Jinan, Shandong 250012, P.R. China.
Tao
T
Peng
Department of Nephrology, Affiliated Hospital of Binzhou Medical School, Yantai, Shandong 264003, P.R. China.
Xiangdi
X
Chang
Department of Nephrology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
Jie
J
Wang
Department of Pathology, Shandong University Qilu Hospital, Jinan, Shandong 250012, P.R. China.
Junhui
J
Zhen
Department of Nephrology, Shandong University Qilu Hospital, Jinan, Shandong 250012, P.R. China.
Xiangdong
X
Yang
Department of Nephrology, Shandong University Qilu Hospital, Jinan, Shandong 250012, P.R. China.
Zhao
Z
Hu
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D008565:Membrane Proteins; D020011:Protective Agents; C113267:nephrin; D013311:Streptozocin; D003404:Creatinine; D016559:Tacrolimus