The Mechanism And Kidney-targeted Delivery Of Tanshinone Protect Against Cadmium-induced Renal Injury

1 The Mechanism of Tanshinone in Treating Cadmium-Induced Kidney InjuryBackground:Occupational and environmental pollution of cadmium affects all organs of the human body.In the kidney,proximal renal tubules are the main accumulation sites of cadmium.Therefore,proximal renal tubular cells are a good model for the study of cadmium-induced renal injury.Tanshinone II A can improve renal microcirculation,protect vascular endothelial cells in the kidney,clearing oxygen free radical and lipid oxidation resistance,the prevention and treatment of kidney pellet hardening and so on,but its mechanism of cadmium to kidney damage is not clear.Objective:To investigate the protective role and mechanism of tanshinone on Cd-induced kidney injury.Methods:Cadmium-exposed renal tubular epithelial cells were used as models in vitro,and mice intraperitoneally injected with cadmium chloride were used as models in vivo.The cells were divided into four groups:normal group,Cd group,normal group plus tanshinone group,and Cd plus tanshinone group.The mice were divided into 3 groups:the normal group,the cadmium-stained group,and the cadmium-danshinone group.The cell experiment explored the mechanism by detecting cell activity,cell apoptosis,oxidative stress,and protein expression.Results:The results of cell activity test showed that the cell activity of Cd group was significantly lower than that of normal group and the Calcein staining gets the similar results.The results of WB show that the Cd can increase the NLRP3 expression in renal tubular epithelial cells and tanshinone can reverse this phenomenon.Consistent with the in vitro experiment,after intraperitoneal injection of Cd,antioxidant capacity of rats decreased,kidney damage occurred,and the expression of NLRP3 in the kidney increased,while tanshinone can improve the above performance.Conclusion:Tanshinone can reduce Cd induced NRK-52E cell injury,and its mechanism may be related to inhibition of oxidative stress and regulation of NLRP3 signaling pathway.2 Tanshinone-Loaded Nanoparticles Protect Against Cadmium-Induced Renal InjuryBackground:Liposomes is composed of an orderly lipid bilayer of the internal water phase of single layer or multilayer vesicles,which is like the biological membrane bilayer structure.It has excellent biocompatibility,high efficiency,low toxic and other characteristics and it can increase the stability and solubility of the drug,slow releasing medicine in vivo,and can effectively improve the bioavailability of drugs.In this study,liposomes modified with chitosan were used to deliver targeted drugs to the kidney.It may provide a new idea for the accurate treatment of kidney diseases.Objective:To study the the characteristics and protective role of Tanshinone-loaded nanoparticles.Methods:The prescribed amount of lecithin,cholesterol and tanshinone were weighed and dissolved in 16mL anhydrous ethanol and 4ml dichloromethane.The anhydrous ethanol was removed by decompressed steam in a 250mL round-bottom flask to form a uniform and transparent film.Deionized water was added to the lipid film obtained by evaporation,and the water bath continued to rotate for 30min at atmospheric pressure to hydrate the film.After the ice bath ultrasound 5 min,the microporous filter membrane was filtered to obtain the composite liposome with blue opalescence,and the particle size distribution was determined.Methanol was added to demulsify,centrifuged,supernatant was absorbed,and the encapsulation rate was determined by ultraviolet spectrophotometer.Tanshinone liposomes modified by chitosan were prepared by post-insertion method.The morphology was confirmed by SEM and TEM.The kidney targeting effect of the vector and its modified liposome was studied by injection and fluorescence imaging in mice.The pharmacodynamics of tanshinone liposomes were studied in cadmium-stained acute kidney injury mice.Results:The drug loading system was spherical nanoparticles with an average particle size of(48.49±0.61 nm).It showed that there was no sudden release of the drug carrier system under the physiological pH condition.Near-infrared fluorescence imaging showed that the drug carrier system was more distributed to the kidney than free drugs,and animal experiments showed that it had better kidney protection than free drugs.Conclusion:The chitosan-modified tanshinone liposome prepared in this study is expected to achieve renal targeted delivery and therapy.