Department of Medical Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou 730000, China.
Int J Mol Sci. 2022 Apr 27;23(9):4866. doi: 10.3390/ijms23094866.
Concurrent exposure to ionizing radiation (IR) and psychological stress (PS) may affect the development of adverse health consequences in scenarios such as space missions, radiotherapy and nuclear accidents. IR can induce DNA damage and cell apoptosis in the kidneys, thus potentially leading to renal fibrosis, which is the ultimate outcome of various chronic progressive nephropathies and the morphological manifestation of a continuous coordinated response after renal injury. However, little is known regarding the effects of concurrent IR exposure and PS on renal damage, particularly renal fibrosis. In this study, using a chronic restraint-induced PS (CRIPS) model, we exposed -heterozygous mice to total body irradiation with 0.1 or 2 Gy Fe ions on the eighth day of 28 consecutive days of a restraint regimen. At the end of the restraint period, the kidneys were collected. The histopathological changes and the degree of kidney fibrosis were assessed with H&E and Masson staining, respectively. Fibronectin (FN) and alpha smooth muscle actin (α-SMA), biomarkers of fibrosis, were detected by immunohistochemistry. Analysis of 8-hydroxy-2 deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, was performed with immunofluorescence, and terminal deoxynucleotidyl transferase-mediated nick end labeling assays were used to detect apoptotic cells. Histopathological observations did not indicate significant structural damage induced by IR or CRIPS + IR. Western blotting revealed that the expression of α-SMA was much higher in the CRIPS + IR groups than the CRIPS groups. However, no differences in the average optical density per area were observed for FN, α-SMA and 8-OHdG between the IR and CRIPS + IR groups. No difference in the induction of apoptosis was observed between the IR and CRIPS + IR groups. These results suggested that exposure to IR (0.1 and 2 Gy Fe ions), 28 consecutive days of CRIPS or both did not cause renal fibrosis. Thus, CRIPS did not alter the IR-induced effects on renal damage in Trp53-heterozygous mice in our experimental setup.
同时暴露于电离辐射（IR）和心理应激（PS）可能会影响太空任务、放射治疗和核事故等情况下不良健康后果的发展。IR 可诱导肾脏中的 DNA 损伤和细胞凋亡，从而可能导致肾纤维化，这是各种慢性进行性肾病的最终结果，也是肾脏损伤后持续协调反应的形态表现。然而，对于同时暴露于 IR 和 PS 对肾脏损伤的影响，特别是肾纤维化的影响，知之甚少。在这项研究中，我们使用慢性束缚诱导的 PS（CRIPS）模型，在 28 天连续束缚的第 8 天，用 0.1 或 2 Gy Fe 离子对 -杂合子小鼠进行全身照射。在束缚期结束时，收集肾脏。用 H&E 和 Masson 染色分别评估组织病理学变化和肾脏纤维化程度。用免疫组化检测纤维化生物标志物纤维连接蛋白（FN）和α平滑肌肌动蛋白（α-SMA）。用免疫荧光法分析 8-羟基-2-脱氧鸟苷（8-OHdG），一种氧化 DNA 损伤的生物标志物，并使用末端脱氧核苷酸转移酶介导的缺口末端标记法检测凋亡细胞。组织病理学观察结果并未表明 IR 或 CRIPS+IR 引起明显的结构损伤。Western blot 显示，CRIPS+IR 组的 α-SMA 表达明显高于 CRIPS 组。然而，IR 和 CRIPS+IR 组之间 FN、α-SMA 和 8-OHdG 的平均光密度/面积没有差异。IR 和 CRIPS+IR 组之间凋亡的诱导没有差异。这些结果表明，暴露于 IR（0.1 和 2 Gy Fe 离子）、28 天连续的 CRIPS 或两者都不会导致肾纤维化。因此，在我们的实验设置中，CRIPS 没有改变 Trp53-杂合子小鼠中 IR 对肾脏损伤的影响。
