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首页> 外文期刊>Current therapeutic research, clinical and experimental. >Differential Effects of Cyclosporin and Etanercept Treatment on Various Pathologic Parameters in a Murine Model of Irradiation-Induced Mucositis
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Differential Effects of Cyclosporin and Etanercept Treatment on Various Pathologic Parameters in a Murine Model of Irradiation-Induced Mucositis

机译：环孢素和依那西普治疗对辐射诱发的粘膜炎小鼠模型中各种病理参数的不同作用

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BACKGROUND: Radiation therapy is the most prescribed treatment for many oncologic indications. One of its common side effects is mucositis with hallmark apoptosis in the intestinal crypt and diarrhea.OBJECTIVE: We investigated the potential beneficial effects of etanercept and cyclosporin treatment during radiation exposure. The effects of these drugs on intestinal apoptosis, long-term weight loss, diarrhea severity, and survival were examined.METHODS: For acute observation studies, animals pretreated with phosphate buffer saline (PBS) vehicle, either etanercept, or cyclosporin were challenged with either 1 Gy or 13 Gy irradiation and sacrificed 6 hours later. The animals' small intestines were then harvested for histologic analysis. For chronic survival studies, 14.5 Gy irradiation was applied. Etanercept or cyclosporin treatments were given 15 minutes before the irradiation, followed by daily administration.RESULTS: At 6 hours postirradiation the maximum apoptotic index observed in the small intestine was ~25% for both 1 Gy and 13 Gy irradiation. Etanercept and cyclosporin pretreatment had no effect on the irradiation-induced apoptosis. During chronic observation, the rate of weight loss was similar in all test groups. At 7 days postirradiation, the weight loss in phosphate buffered saline-treated control, etanercept, and cyclosporin groups reached a maximum at 19%, 24%, and 31.8%, respectively. The weight lost in the cyclosporin group was significantly higher than in the control group. Neither treatment reduced the severity of diarrhea, but cyclosporin increased the survival rate. Sixty percent of cyclosporin-treated animals survived compared with 27% in the PBS-treated control group and 47% in the etanercept-treated group. Serum tumor necrosis factor-a levels, a biomarker for both etanercept's mechanism of action and treatment efficacy, was inhibited by etanercept throughout the study, but cyclosporin only showed an inhibitory effect at 48 hours postirradiation.Conclusions: Our study demonstrates that cyclosporin increases the survival rate of irradiated animals without affecting parameters such as intestinal histology, weight loss, and diarrhea severity.
机译：背景：放射治疗是许多肿瘤适应症的最处方治疗。它的常见副作用之一是在肠隐窝和腹泻中具有标志性细胞凋亡的粘膜炎。目的：我们研究了依那西普和环孢菌素治疗在放射线照射期间的潜在有益作用。方法：对于急性观察研究，用磷酸盐缓冲盐水（PBS）媒介物（依那西普或环孢菌素）预处理的动物均受到挑战，以进行急性观察研究1 Gy或13 Gy辐射，并在6小时后处死。然后收集动物的小肠用于组织学分析。对于慢性存活研究，应用14.5 Gy照射。照射前15分钟给予Etanercept或环孢菌素治疗，然后每日给药。结果：照射后6小时，在1 Gy和13 Gy照射下，小肠中观察到的最大细胞凋亡指数均为〜25％。依那西普和环孢菌素预处理对辐射诱导的细胞凋亡没有影响。在长期观察期间，所有测试组的体重减轻率均相似。辐照后第7天，磷酸盐缓冲液处理的对照组，依那西普和环孢菌素组的体重减轻分别达到最大，分别为19％，24％和31.8％。环孢菌素组的体重减轻明显高于对照组。两种方法都不能减轻腹泻的严重程度，但是环孢菌素可以提高生存率。 60％的环孢菌素治疗动物存活，而PBS处理的对照组为27％，依那西普治疗组为47％。在整个研究中，血清肿瘤坏死因子-α水平（既是etanercept的作用机理又是治疗效果的生物标志物）均被etanercept抑制，但环孢菌素仅在照射后48小时显示出抑制作用。结论：我们的研究表明环孢菌素可提高生存不影响肠道组织学，体重减轻和腹泻严重程度等参数的动物辐照速度

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