Ytterbrink Charlotte, Simonsson Klara, Shubbar Emman, Gram Magnus, Helou Khalil, Forssell-Aronsson Eva
Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
Sahlgrenska Center for Cancer Research, Sahlgrenska Academy at the University of Gothenburg, Box 425, SE-405 30 Gothenburg, Sweden.
Radiat Prot Dosimetry. 2025 Aug 26;201(13-14):877-886. doi: 10.1093/rpd/ncaf055.
The antioxidant α1-microglobulin (A1M) has been suggested as kidney protector during 177Lu-octreotate treatment. The aim of this work was to evaluate apoptotic-related transcript expression in kidney cortex and medulla following injection of 177Lu-octreotate and/or A1M. Mice were injected with 177Lu-octreotate, A1M, or 177Lu-octreotate + A1M. Control groups received PBS or vehicle solution. Animals were killed after 24 hours or 7 d. mRNA was isolated from kidney medulla and cortex. Expression of 84 apoptosis-related genes was assessed by q-PCR. Gene expression profiles in kidney cortex were generally similar in the 177Lu-octreotate and 177Lu-octreotate + A1M groups. This was also seen in kidney medulla at 24 hours, but at 7 d anti-apoptotic response of A1M was observed. Altogether, 177Lu-octreotate exposure induced pro-apoptotic response (e.g. Apaf1, Bax, and Tnfrsf10b genes) in kidney medulla and cortex. A1M co-administration did not inhibit pro-apoptotic response in kidney cortex, while A1M initiated pro-survival mechanisms in kidney medulla.
抗氧化剂α1-微球蛋白(A1M)被认为是177Lu-奥曲肽治疗期间的肾脏保护剂。这项工作的目的是评估注射177Lu-奥曲肽和/或A1M后肾皮质和髓质中凋亡相关转录本的表达。给小鼠注射177Lu-奥曲肽、A1M或177Lu-奥曲肽+A1M。对照组接受磷酸盐缓冲液(PBS)或赋形剂溶液。24小时或7天后处死动物。从肾髓质和皮质分离mRNA。通过定量聚合酶链反应(q-PCR)评估84个凋亡相关基因的表达。177Lu-奥曲肽组和177Lu-奥曲肽+A1M组肾皮质中的基因表达谱总体相似。在24小时时肾髓质中也观察到这种情况,但在7天时观察到A1M的抗凋亡反应。总之,暴露于177Lu-奥曲肽会在肾髓质和皮质中诱导促凋亡反应(如凋亡蛋白酶激活因子1(Apaf1)、促凋亡蛋白Bax和肿瘤坏死因子受体超家族成员10b(Tnfrsf10b)基因)。联合给予A1M不会抑制肾皮质中的促凋亡反应,而A1M会在肾髓质中启动促生存机制。