重组人白细胞介素-12对胰腺癌放射治疗防护作用的研究

Study on Radiation Protection Effect of Recombinant Human Interleukin-12 in Radiotherapy for Pancreatic Cancer

[目的]探讨重组人白细胞介素-12（recombinant human interleukin-12,rhIL-12）在胰腺癌放射治疗放射防护中发挥的作用。[方法]回顾性分析52例胰腺癌患者,根据治疗方式分为单纯放疗组和rhIL-12＋放疗组。两组患者均采用射波刀治疗,放射剂量30~35Gy,r IL-12＋放疗组放疗后予以150ng/kg rhIL-12干预治疗。两组分别于0h、12h、3d、7d、14d、21d、28d采用流式细胞术检测两组患者细胞免疫功能相关指标CD4/CD8比值、CD45、CD56数值变化;ELISA法检测血清细胞因子IFN-γ表达水平;分析评价两组患者外周血细胞计数变化、近期治疗疗效和胃肠道相关不良反应。[结果]rhIL-12＋放疗组患者免疫相关分子CD4/CD8比值、CD45和CD56表达12h内均存在一过性降低现象,随治疗时间的推移逐渐回升,于治疗第14d达到峰值且恢复,改善趋势明显优于单纯放疗组（P〈0.05）;细胞因子IFN-γ表达随时间变化逐渐递增,于14d达峰值,较单纯放疗组具有显著性差异（P〈0.05）。血液标本检测显示两组患者治疗前红细胞（RBC）、白细胞（WBC）、血小板（PLT）、中性粒细胞（NEUT）计数以及血红蛋白（Hb）含量均无显著性差异（P〉0.05）;在治疗14d时rhIL-12＋放疗组患者WBC、PLT和NEUT计数较单纯放疗组均具显著性差异（P〈0.05）,而RBC计数和Hb含量则差异无统计学意义（P〉0.05）;rhIL-12＋放疗组患者近期治疗疗效显著（P=0.046）;两组患者胃肠道不良反应主要表现为恶心呕吐和腹泻,rhIL-12＋放疗组发生率均低于单纯放疗组（P=0.001;P=0.012）。[结论]rhIL-12可有效地促进胰腺癌放射治疗患者造血功能和免疫机能的恢复和重建,并能降低放射治疗不良反应的发生率,提高治疗疗效。

[Objective] To investigate the role of recombinant human interleukin-12（rhIL-12） on radiation protection in radiotherapy for pancreatic cancer. [Methods] The clinical data of 52 cases with pancreatic cancer was analyzed retrospectively. Patients were divided into two groups according to treatment method：radiotherapy alone group and rhIL-12 plus radiotherapy group. The patients in two groups both received Cyber Knife radiosurgery with 30 to 35 Gy. The patients in rhIL-12 plus radiotherapy group were treated with r IL-12 with the dose of 150ng/kg additionally.CD4/CD8 ratio,the number of CD45 and CD56 were detected by flow cytometry（FCM） at 0h,12 h,3d,7d,14 d,21d and 28 d,respectively. The level of IFN-γ was analyzed by ELISA. The changes of peripheral blood cell counts,short-term response and gastrointestinal tract toxicities were compared between the two groups. [Results] CD4/CD8 ratio,CD45 and CD56 showed a transient decreasing within 12 h in rhIL-12 plus radiotherapy group,and then significantly increased with the lapse of time. Subsequently,the expressions of them reached peak level at the 14th day and the trend of improvement was significantly better than that in radiotherapy alone group（P0.05）. The expression of IFN-γ gradually increased with the lapse of time and reached peak level at the 14th day which had significant difference compared to radiotherapy alone group（P0.05）. There was no significant difference in red blood cells（RBC）,white blood cells（WBC）,platelet（PLT）,neutrophil（NEUT） and hemoglobin（Hb） between the two groups before treatment（P0.05）. The levels of WBC,PLT and NEUT had significant difference at the 14th day in rhIL-12 plus radiotherapy group compared to radiotherapy alone group（P0.05）. While there was no statistical significance in the levels RBC and Hb（P0.05）. The short-term response in rhIL-12 plus radiotherapy group was significant（P =0.046）. Gastrointestinal tract toxicities in two groups were mainly for nausea and vomiting and diarrhea. Patients in the rhIL-12 plus radiotherapy group showed a lower incidence than that in radiotherapy alone group（P=0.001;P=0.012）. [Conclusion]RhIL-12 might effectively improve recovery of hematopoiesis and immune reconstitution,reduce the toxicities and enhance the clinical efficacies in patients with pancreatic cancer.