【摘要】 目的：探讨右美托咪定通过抑制铁死亡下调RNA结合基元蛋白3(RBM3)降低阿霉素诱导的心肌毒性。方法：将SPF级别2月龄SD大鼠随机分组，分为对照组（Control）、阿霉素组（Adr）、阿霉素+右美托咪定组（Adr+Dex）、阿霉素+右美托咪定+铁死亡激动剂组（Adr+Dex+Era）。采用Adr组隔日给药2.5 mg/kg，共计给药6次；Adr+Dex组Adr隔日给药，并每天给予Dex 50μg/kg，共给予19次；Adr+Dex+Era(Erastin，铁死亡激动剂)组按相同给药方式给予Adr和Dex，并在14 d隔日给予10mg/kg Era，共计3次。Control组给予等体积生理盐水及DMSO溶剂。第19 d麻醉处死取心室行天狼星检测纤维化情况，免疫组化检测RBM3表达情况、普鲁士蓝染色检测铁沉积，Western blot及PCR检测RBM3表达情况。结果：与Adr组比较，Adr+Dex组明显抑制Adr引起的纤维化增加，减少Adr引起的RBM3在核酸及蛋白质水平的上调，改善Adr引起的铁沉积。铁死亡激动剂Era再次逆转了Dex的保护作用，RBM3的m RNA及蛋白质表达均下调，细胞活性也同步下降。人源细胞CCK-8实验证实，与Control组比较，Adr组明显降低细胞活性；而Adr+Dex组与Adr组比较无明显变化；Dex单药组与Control组比较无影响。结论：Dex在不影响Adr抗肿瘤作用的前提下，抑制铁死亡发生，下调RBM3表达，改善阿霉素诱导的心肌毒性。更多还原

【Abstract】 AIM: To investigate the effect of dexmedetomidine(Dex) on reducing doxorubicin-induced cardiotoxicity by downregulating RNA-binding motif protein 3(RBM3) through inhibiting ferroptosis. METHODS: Two-month-old SPF SD rats were randomly divided into control group(Control), adriamycin group(Adr), doxorubicin + dexmeadriamycin group(Adr + Dex), and adriamycin +dexmedetomidine + ferroptosis agonist group(Adr +Dex + Era). The Adr group was given 2.5 mg/kg of Adr every other day for a total of 6 times; the Adr+Dex group was given Adr every other day and Dex50 μg/kg every day for a total of 19 times; the Adr+Dex+Era group was given Adr and Dex in the same way, and 10 mg/kg of Era was given every other day for 14 days for a total of 3 times. The control group was given equal volumes of normal saline and DMSO solvent. The rats were anesthetized and sacrificed on day 19, and the ventricles were removed for Sirius to detect fibrosis, immunohistochemistry to detect RBM3 expression, Prussian blue staining to detect iron deposition, Western blotting and PCR to detect RBM3 expression. RESULTS: Compared with the Adr group, the Adr+Dex group significantly inhibited the increase of fibrosis caused by Adr, reduced the upregulation of RBM3 caused by Adr, and improved the iron deposition caused by Adr. The ferroptosis agonist Era reversed the protective effect of Dex again. CONCLUSION:Dex inhibits ferroptosis, downregulates RBM3 expression, and improves adriamycin-induced myocardial toxicity without affecting the anti-tumor effect of Adr.更多还原