摘要
Abstract
Objective To explore the mechanism of tacrolimus mediating the protective effect on chronic glomerulonephritis(CGN)rats through regulating the expression of microRNA-145-5p(miR-145-5p)and modulating the C-X-C motif chemokine ligand 16/Ras homolog family member A/Rho-associated coiled-coil-containing protein kinase(CXCL16/RhoA/ROCK)pathway.Methods SD rats were randomly divided into the control group(administered an equal volume of 0.9％NaCl),model group(CGN model+equal volume of 0.9％NaCl),experimental group(CGN model+3 mg·kg-1·d-1 tacrolimus)and combined group(experimental group+tail vein injection of 140 nmol·L-1 miR-145-5p antagomir).Enzyme-linked immunosorbent assay was used to measure 24-hour urinary protein(PRO),blood urea nitrogen(BUN),and serum creatinine(SCr)levels.Real-time quantitative polymerase chain reaction was used to detect the relative expression level of miR-145-5p in rat kidney tissue;Western blotting was used to determine protein expression levels.Results The 24-hour PRO levels in the control,model and experimental groups were(7.44±2.16),(85.29±17.35)and(49.81±9.52)mg,respectively;the BUN levels were(5.82±1.03),(9.65±1.78)and(6.97±1.14)mmol·L-1,respectively;the SCr levels were(46.31±7.69),(93.57±16.94)and(58.72±8.36)μmol·L-1,respectively.The relative expression levels of miR-145-5p in the control,model,experimental and combined groups were 1.00±0.14,0.56±0.07,0.83±0.12 and 0.68±0.09,respectively;the TNF-α levels were(116.42±14.53),(237.56±26.18),(164.79±18.35)and(205.12±21.64)pg·mL-1,respectively;the IL-1β levels were(15.76±1.84),(52.41±6.27),(21.35±2.92)and(43.63±4.58)pg·mL-1,respectively;the IL-6 levels were(26.28±3.47),(71.53±8.64),(38.92±5.06)and(59.78±6.21)pg·mL-1,respectively;the CXCL16 expression levels were 1.00±0.12,1.62±0.17,1.23±0.14 and 1.45±0.15,respectively.Statistical analysis revealed significant differences between the model group and the control group,between the experimental group and the model group,and between the combined group and the experimental group for these indicators(P＜0.05,P＜0.01,P＜0.001).Conclusion Tacrolimus can upregulate miR-145-5p,activate the CXCL16/RhoA/ROCK pathway,reduce inflammatory factors,and improve kidney damage in CGN rats.关键词
他克莫司/微小分子核糖核酸145-5p/CXC配体16/Rho相关蛋白激酶/慢性肾小球肾炎Key words
tacrolimus/microRNA-145-5p/CXC ligand 16/Rho-associated protein kinase/chronic glomerulone-phritis分类
医药卫生
