Combination of different drugs can enhance prevention of CIAKI through inhibition of endoplasmic reticulum stress-induced apoptotic pathway

Abstract

Introduction: Contrast-induced acute kidney injury(CIAKI) is an important clinical complication that occurs after the application of contrast in percutaneous coronary intervention. The pathogenesis of CIAKI is complex. Studies have shown that the cell apoptosis induced by endoplasmic reticulum stress (ERS) play an important role in the renal tubular injury of CIAKI. It was suggested that atorvastatin, probucol and alprostadil can inhibit renal tubular cell apoptosis to prevent CIAKI. However, there is no specific research about the above effect of the drug combination. Therefore, this study intends to establish the rat CIAKI model by meglumine diatrizoate and add drug intervention, to compare the influence of combined drugs with the single atorvastatin for CIAKI by inhibiting ERS specific molecular chaperone. Method and Result: 50 Wistar rats were randomly divided into 5 groups: Group A (atorvastatin group, n=10); Group P (probucol + atorvastatin group, n=10); Group Q (alprostadil + atorvastatin group, n=10); Group NC (contrast group, n=10); Group N (control group, n=10). After treated with meglumine diatrizoate and different drugs, the kidneys were obtained for HE, TUNEL staining and real-time RT-PCR, western blot, immunohistochemitry to detect the expression of nucleic acid and protein levels of GRP78, GADD153/CHOP, Caspase-12 in the ERS pathways. Group NC has the significantly highest creatinine rise rate, expression level of protein and nucleic acid in the five groups, with the most serious cell injury and apoptosis in HE and TUNEL staining. Compared with the single atorvastatin group, creatinine rise rate and expression of protein in the combined medication groups were decreased to some extent, whose histological morphology was also improved. This was especially evident in the group Q. Conclusion: The renal cell apoptosis induced by ERS pathway may play an important role in pathogenesis of CIAKI induced by meglumine diatrizoate. Atorvastatin, probucol and alprostadil can prevent the occurrence of CIAKI, may through the inhibition of cell apoptosis induced by ERS pathway. The protective effect for CIAKI of probucol or alprostadil combined with atorvastatin may be stronger than the single atorvastatin through ERS pathway, with the more effect of the combination of alprostadil and atorvastatin.