Wang Xuan, Han Shan, Zhao Lili, Cong Hongliang
Department of Cardiac Surgical Intensive Care Unit, Yantai Yuhuangding Hospital, Qingdao University Affiliated Hospital, No.20 of Yuhuangding East Road, Yantai, 264000, Shandong, China.
Department of Cardiology, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Tianjin, 300121, China.
Sci Rep. 2024 Dec 30;14(1):32074. doi: 10.1038/s41598-024-83741-5.
Contrast-induced acute kidney injury (CIAKI) is an important clinical complication that occurs after the application of contrast agent in percutaneous coronary intervention. The pathogenesis of CIAKI is complex. Studies have shown that cell apoptosis induced by endoplasmic reticulum stress (ERS) plays an important role in renal tubular injury in CIAKI. These findings suggest that atorvastatin, probucol and alprostadil can inhibit renal tubular cell apoptosis to prevent CIAKI. However, there is no specific research on the above effects of drug combinations. Therefore, this study aimed to establish a rat CIAKI model with meglumine diatrizoate and add drug intervention to compare the influence of combined drugs with that of atorvastatin alone on CIAKI via the inhibition of ERS-specific molecular chaperones. Fifty Wistar rats were randomly divided into 5 groups: Group A + CC (atorvastatin group, n = 10); Group PA + CC (probucol + atorvastatin group, n = 10); Group AA + CC (alprostadil + atorvastatin group, n = 10); Group PCC (contrast group, n = 10); and Group NCC (control group, n = 10). Among the five groups, Group PCC presented the significantly highest creatinine increase rate and protein and nucleic acid expression levels, with the most severe cell injury and apoptosis observed via HE and TUNEL staining. Compared with those in the atorvastatin group, the rate of increase in creatinine and protein expression in the combined treatment groups were decreased to some extent, and the histological morphology was also improved. This was especially evident in Group AA + CC. Renal cell apoptosis induced by the ERS pathway may play an important role in the pathogenesis of CIAKI induced by meglumine diatrizoate. Atorvastatin, probucol and alprostadil can prevent the occurrence of CIAKI, and the ERS-induced apoptosis pathway is involved in this mechanism. The protective effect of probucol or alprostadil combined with atorvastatin on CIAKI may be stronger than that of atorvastatin alone, with a greater effect of the combination of alprostadil and atorvastatin.
对比剂诱导的急性肾损伤（CIAKI）是经皮冠状动脉介入治疗中应用对比剂后发生的一种重要临床并发症。CIAKI的发病机制复杂。研究表明，内质网应激（ERS）诱导的细胞凋亡在CIAKI的肾小管损伤中起重要作用。这些发现提示阿托伐他汀、普罗布考和前列地尔可抑制肾小管细胞凋亡以预防CIAKI。然而，对于上述药物组合的上述作用尚无具体研究。因此，本研究旨在建立用泛影葡胺诱导的大鼠CIAKI模型并进行药物干预，通过抑制ERS特异性分子伴侣来比较联合用药与单用阿托伐他汀对CIAKI的影响。将50只Wistar大鼠随机分为5组：A组+CC（阿托伐他汀组，n = 10）；PA组+CC（普罗布考+阿托伐他汀组，n = 10）；AA组+CC（前列地尔+阿托伐他汀组，n = 10）；PCC组（对比剂组，n = 10）；NCC组（对照组，n = 10）。在这五组中，PCC组的肌酐升高率以及蛋白质和核酸表达水平显著最高，通过苏木精-伊红（HE）染色和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色观察到的细胞损伤和凋亡最为严重。与阿托伐他汀组相比，联合治疗组的肌酐升高率和蛋白质表达有所降低，组织形态学也有所改善。这在AA组+CC中尤为明显。ERS途径诱导的肾细胞凋亡可能在泛影葡胺诱导的CIAKI发病机制中起重要作用。阿托伐他汀、普罗布考和前列地尔可预防CIAKI的发生，且ERS诱导的凋亡途径参与了这一机制。普罗布考或前列地尔与阿托伐他汀联合应用对CIAKI的保护作用可能强于单用阿托伐他汀，其中前列地尔与阿托伐他汀联合应用的效果更佳。
