188铼辐射抑制血管平滑肌细胞增殖研究

目的：探讨放射性核素¹⁸⁸铼（¹⁸⁸Re）对培养平滑肌细胞增殖的作用及其机制。方法：应用¹⁸⁸Re β射线进行培养平滑肌细胞的内辐射。通过细胞计数、再增殖试验、[³H]-TdR掺入试验、流式细胞术细胞周期分析、免疫细胞化学及细胞存活率检测等方法，观察辐射抑制平滑肌细胞增殖的有效及最佳剂量、有效抑制时间、细胞增殖率变化、细胞周期分布、细胞存活率及其相关基因表达。结果：5.2 Gy剂量辐射，50%以上平滑肌细胞增殖受抑，细胞增殖率为46%；20.6 Gy剂量辐射，DNA合成抑制率达92%，增殖期细胞占3%；辐射后2周未见细胞再增殖，<20.6 Gy辐射未见细胞存活力下降；辐射后P53表达升高，PCNA表达降低。结论：¹⁸⁸Re β辐射对平滑肌细胞增殖抑制有效且持久半数有效剂量为5 Gy最佳辐射剂量为20 Gy。低剂量辐射抑制平滑肌细胞增殖的主要机制为损伤细胞分裂增殖能力。P53及PCNA调控辐射抑制细胞增殖过程。

Effects of radiation from 188Re on smooth muscle cell proliferation

AIM: Although endovascular radiotherapy inhibits neointimal hyperplasia, the exact alterations induced by β-particles irradiation remain to be elucidated. The objective of this study was to investigate the ability and the cellular mechanism of local β^-particles emission from ¹⁸⁸Re to inhibit vascular smooth muscle cells (SMCs). METHODS: The SMCs in vitro were irradiated by ¹⁸⁸Re with single doses of 2.6 Gy-25.8 Gy. The effects of β-particles on SMCs, such as effective irradiate doses, the period of inhibition for SMCs proliferation, the changes of cell proliferation rate and DNA synthesis rate, cell cycle progression and related gene expression, were investigated by cell count, [³H]-TdR incorporation, cell cycle progression analysis, cell viability and immunocytochemistry, respectivecy. RESULTS: β-particles irradiation with dose of 5.2 Gy could inhibit significantly SMCs proliferation. At dose of 20.6 Gy DNA synthesis inhibitory rate was 92%, SMCs proliferation rate was only 3%. Renoval of ¹⁸⁸Re did not abolish the inhibitory effects of β-particles on SMCs proliferation. The expression of P53 was up regulation and PCNA was down regulation after irradiation. CONCLUSION: β-particles from ¹⁸⁸ Re was significantly effective and permanent in inhibiting SMCs proliferation, and inhibitory effect was in dose-dependet manner ED50was 5 Gy, the best dose to inhibit SMCs proliferation was 20 Gy. β-particles irradiation induced SMCs to occur G₀/G₁ arrest, damaged the ability of SMCs reproliferation and led to cell clonogenic death. P53 and PCNA had regulatiory effects on SMCs proliferation after β-particles irradiation.