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目的 用荷瘤和无瘤大鼠的放射性肺损伤模式评价阿米福汀 (Amifostine,WR 2 72 1)的放射性肺损伤保护作用。方法 选 15 0~ 16 0g的Fisher 34 4雌性大鼠 ,在右后胸壁种植R32 30AC人乳腺癌细胞株 ,肿瘤长至直径为 1.0~ 1.5cm时和无肿瘤大鼠随机进入实验组。用 4MVX射线、剂量DT35Gy5分次 5d照射右全肺 ,每次照射前 30min腹腔内注射Amifostine(15 0mg kg)。照射后观测呼吸频率、肿瘤大小和转化生长因子 (TGF β1 )水平。当出现呼吸困难伴体重下降时 ,终止观察 ,否则在 6个月后终止观察。肺组织进行羟脯胺酸和TGF β1 表达等生物学检测。结果 治疗后第 3d体重下降明显 ,照射加Amifostine(15 % )和单用Amifostine(11% )与单纯放射 (7% )间有明显的差别。肿瘤生长延迟和肿瘤生长情况及因肿瘤肺转移死亡贡献生存率 ,用药与未用药者相似。无瘤大鼠单纯照射组的平均呼吸频率增加早 (第 9周开始 )、幅度高 (12 5~ 12 7次 min) ,照射加药组在第 12周开始 ,115~ 118次 min(P <0 .0 0 1)。单纯照射组羟脯胺酸含量明显高于照射加amifostine组 (P =0 .0 42 )、单用药组和对照组 (P <0 .0 1)。血浆TGF β1 含量在照射后 1~ 3个月增加、2个月达高峰 ,单放组的TGF β1 含量[(5 .32± 1.2 1)ng mL]明显高于用药组
Objective To evaluate the protective effect of amifostine (WR 2 72 1) against radiation-induced lung injury in radiation-induced lung injury models in tumor-bearing and tumor-free rats. METHODS: The Fisher 34 4 female rats were selected from 150 to 160 g and R32 30AC human breast cancer cell lines were implanted in the right posterior chest wall. The tumors grew to 1.0-1.5 cm in diameter and randomly entered the experimental group. Right lungs were irradiated with 4MV X-rays and doses of DT35Gy5 for 5 days. Amifostine (15 0 mg kg) was injected intraperitoneally 30 minutes before each irradiation. Respiratory frequency, tumor size, and transforming growth factor (TGFβ1) levels were observed after irradiation. When dyspnea and weight loss occurred, the observation was terminated, otherwise observation was terminated after 6 months. Lung tissue was subjected to biological tests for the expression of hydroxyproline and TGFβ1. Results The body weight decreased significantly on the 3rd day after treatment. The difference between irradiation plus Amifostine (15 %) and Amifostine alone (11%) and radiotherapy alone (7%) was significant. Tumor growth delay and tumor growth and survival due to metastasis to lung metastases contributed to the survival rate. Drug use was similar to that of untreated patients. The mean respiratory rate in the group irradiated with tumor-free rats was earlier (starting at the 9th week) and higher (12 5 to 12 7 min). The irradiation group started at the 12th week and 115-118 min (P < 0 .0 0 1). The levels of hydroxyproline in the irradiation alone group were significantly higher than those in the irradiation plus amifostine group (P = 0.042), single-agent group, and control group (P < 0.01). Plasma TGFβ1 levels increased 1 to 3 months after irradiation and peaked at 2 months. TGFβ1 content in the radiotherapy group was significantly higher than that of the drug group (5.32±1.21 ng mL).