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Abstract：
BACKGROUND: Radiotherapy is a primary local treatment for tumors, yet it may lead to complications such as radiation-induced heart disease (RIHD). Currently, there is no standardized approach for preventing RIHD. Dexmedetomidine (Dex) is reported to have cardio-protection effects, while its role in radiation-induced myocardial injury is unknown. In the current study, we aimed to evaluate the radioprotective effect of dexmedetomidine in X-ray radiation-treated mice.
METHODS: 18 male mice were randomized into 3 groups: control, 16 Gy, and 16 Gy + Dex. The 16 Gy group received a single dose of 16 Gy X-ray radiation. The 16 Gy + Dex group was pretreated with dexmedetomidine (30 µg/kg, intraperitoneal injection) 30 min before X-ray radiation. The control group was treated with saline and did not receive X-ray radiation. Myocardial tissues were collected 16 weeks after X-ray radiation. Hematoxylin-eosin staining was performed for histopathological examination. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was performed to assess the state of apoptotic cells. Immunohistochemistry staining was performed to examine the expression of CD34 molecule and von Willebrand factor. Besides, western blot assay was employed for the detection of apoptosis-related proteins (BCL2 apoptosis regulator and BCL2-associated X) as well as autophagy-related proteins (microtubule-associated protein 1 light chain 3, beclin 1, and sequestosome 1).
RESULTS: The findings demonstrated that 16 Gy X-ray radiation resulted in significant changes in myocardial tissues, increased myocardial apoptosis, and activated autophagy. Pretreatment with dexmedetomidine significantly protects mice against 16 Gy X-ray radiation-induced myocardial injury by inhibiting apoptosis and autophagy.
CONCLUSIONS: In summary, our study confirmed the radioprotective effect of dexmedetomidine in mitigating cardiomyocyte apoptosis and autophagy induced by 16 Gy X-ray radiation.
METHODS: 18 male mice were randomized into 3 groups: control, 16 Gy, and 16 Gy + Dex. The 16 Gy group received a single dose of 16 Gy X-ray radiation. The 16 Gy + Dex group was pretreated with dexmedetomidine (30 µg/kg, intraperitoneal injection) 30 min before X-ray radiation. The control group was treated with saline and did not receive X-ray radiation. Myocardial tissues were collected 16 weeks after X-ray radiation. Hematoxylin-eosin staining was performed for histopathological examination. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was performed to assess the state of apoptotic cells. Immunohistochemistry staining was performed to examine the expression of CD34 molecule and von Willebrand factor. Besides, western blot assay was employed for the detection of apoptosis-related proteins (BCL2 apoptosis regulator and BCL2-associated X) as well as autophagy-related proteins (microtubule-associated protein 1 light chain 3, beclin 1, and sequestosome 1).
RESULTS: The findings demonstrated that 16 Gy X-ray radiation resulted in significant changes in myocardial tissues, increased myocardial apoptosis, and activated autophagy. Pretreatment with dexmedetomidine significantly protects mice against 16 Gy X-ray radiation-induced myocardial injury by inhibiting apoptosis and autophagy.
CONCLUSIONS: In summary, our study confirmed the radioprotective effect of dexmedetomidine in mitigating cardiomyocyte apoptosis and autophagy induced by 16 Gy X-ray radiation.
摘要：
背景：放射治疗是肿瘤的主要局部治疗方法，然而，它可能会导致并发症，如辐射诱发的心脏病（RIHD）。目前,没有预防RIHD的标准化方法。据报道，右美托咪定（Dex）具有心脏保护作用，而其在放射性心肌损伤中的作用尚不清楚。在目前的研究中,我们旨在评估右美托咪定对X线放射治疗小鼠的辐射防护作用.
方法：18只雄性小鼠随机分为3组：对照组，16Gy,和16Gy+Dex。16Gy组接受单剂量16GyX射线辐射。16Gy+Dex组接受右美托咪定预处理（30µg/kg，腹膜内注射）X射线照射前30分钟。对照组用生理盐水治疗，不接受X线照射。X线照射16周后收集心肌组织。苏木精-伊红染色用于组织病理学检查。进行末端脱氧核苷酸转移酶dUTP缺口末端标记染色以评估凋亡细胞的状态。免疫组化染色检测CD34分子和血管性血友病因子的表达。此外,采用westernblot检测凋亡相关蛋白(BCL2凋亡调节因子和BCL2相关X)以及自噬相关蛋白(微管相关蛋白1轻链3、beclin1和螯合体1)。
结果：研究结果表明，16GyX射线辐射导致心肌组织发生明显变化，心肌细胞凋亡增加，并激活自噬。右美托咪定预处理通过抑制细胞凋亡和自噬对16GyX射线辐射诱导的小鼠心肌损伤具有保护作用。
结论：总之，我们的研究证实了右美托咪定减轻16GyX射线辐射诱导的心肌细胞凋亡和自噬的辐射防护作用。
方法：18只雄性小鼠随机分为3组：对照组，16Gy,和16Gy+Dex。16Gy组接受单剂量16GyX射线辐射。16Gy+Dex组接受右美托咪定预处理（30µg/kg，腹膜内注射）X射线照射前30分钟。对照组用生理盐水治疗，不接受X线照射。X线照射16周后收集心肌组织。苏木精-伊红染色用于组织病理学检查。进行末端脱氧核苷酸转移酶dUTP缺口末端标记染色以评估凋亡细胞的状态。免疫组化染色检测CD34分子和血管性血友病因子的表达。此外,采用westernblot检测凋亡相关蛋白(BCL2凋亡调节因子和BCL2相关X)以及自噬相关蛋白(微管相关蛋白1轻链3、beclin1和螯合体1)。
结果：研究结果表明，16GyX射线辐射导致心肌组织发生明显变化，心肌细胞凋亡增加，并激活自噬。右美托咪定预处理通过抑制细胞凋亡和自噬对16GyX射线辐射诱导的小鼠心肌损伤具有保护作用。
结论：总之，我们的研究证实了右美托咪定减轻16GyX射线辐射诱导的心肌细胞凋亡和自噬的辐射防护作用。
