Zhongguo quanke yixue (Jun 2022)
Rosuvastatin Calcium with Metformin Improves Kidney Function in a Rat Model of Diabetes by Regulating the Expression of Glucose Transporter 4
Abstract
Background Rosuvastatin calcium with metformin improves diabetic renal injury, but the mechanism is not yet fully understood. Objective To explore the mechanism of action of rosuvastatin calcium with metformin improving renal injury in a rat model of streptozotocin (STZ) -induced type 2 diabetes mellitus (T2DM) . Methods Forty clean grade Wistar rats were equally randomized into a control group (group C) , a metformin group (group M) , a metformin+low-dose rosuvastatin calcium group (group M+RL) , and a metformin+high-dose rosuvastatin calcium group (group M+RH) from July to October 2021. T2DM model was established for three groups (except for group C) using intraperitoneal injection of STZ. Then drug was administered by intragastric administration to the groups as follows: equal amount of 0.9% sodium chloride solution for group C, metformin (200 mg·kg-1·d-1) for group M, metformin (200 mg·kg-1·d-1) suspension+rosuvastatin calcium (0.42 mg·kg-1·d-1) for group M+RL, and metformin (200 mg·kg-1·d-1) suspension+rosuvastatin calcium (0.83 mg·kg-1·d-1) for group M+RH. Rats were sacrificed after 6 weeks of intervention, while their blood and kidney tissues were collected. The extent of injury of kidney tissues was observed under light microscope after being stained with H&E, and was analyzed using Image-Pro Plus 6.0 after being stained with periodic-acid schiff, and Masson's trichrome, respectively. The expression of glucose transporter 4 (GLUT4) mRNA in the renal tissue was measured by real-time polymerase chain reaction (PCR) , and the protein levels of GLUT4 were detected by Western-blotting. Results Compared with group C, the glomerulus of rats in other three groups showed significant structural damage, accompanied by inflammatory cell infiltration and interstitial fibrosis. Moreover, mRNA expression levels of GLUT4 in these groups were significantly lowered (P<0.05) . Furthermore, the protein levels of GLUT4 in groups M and M+RL were lowered notably (P<0.05) . The mRNA and protein expression levels of GLUT4 in group M+RL or M+RH were higher than those of group M (P<0.05) . In addition, the mRNA and protein expression levels of GLUT4 in M+RH group were higher than those in M+RL group (P<0.05) . Conclusion Rosuvastatin calcium with metformin could reduce inflammatory cell infiltration in glomerular and tubular, alleviate glomerular basement membrane thickening and tubular vacuolar degeneration, delay the interstitial fibrosis development, and increase GLUT4 mRNA and GLUT4 protein expression in STZ-induced T2DM rats. Moreover, higher dose of rosuvastatin calcium showed better effect. Our study indicated that rosuvastatin calcium combined with metformin may achieve a renoprotective effect by regulating the expression of GLUT4 mRNA and protein in T2DM rats, and this effect may be enhanced with the increase in the dose of rosuvastatin calcium.
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