益赛普对大鼠放射性肺损伤中TNF-α的影响

Effect of recombinant human tumor necrosis factor-O receptor on tumor necrosis factor in rats with radiation-induced lung injury

目的观察注射用重组人肿瘤坏死因子受体-抗体融合蛋白(益赛普)对大鼠放射性肺损伤过程中TNF-α的影响,试图寻找一种预防或治疗放射性肺损伤的有效途径。方法 72只雌性SD大鼠随机分为3组:正常对照组、单纯照射组和益赛普治疗组,每组24只。照射组及治疗组动物麻醉后,行直线加速器全胸部照射一次,剂量为25Gy。照射后第一周内,治疗组大鼠腹腔注射益赛普(5mg·kg-1),共计2次。对照组和照射组大鼠注射同等体积的生理盐水。于照射后第1、4、8、和24周处死动物,取部分肺组织行HE染色,观察组织学变化,另提取组织行免疫组化观察组织中TNF-α变化,使用酶联免疫吸附分析法检测血清中TNF-α水平。所有数据采用SPSS统计软件进行方差分析。结果照射组大鼠肺组织血清中TNF-α水平与对照组相比,明显升高,并在第4周时达到顶峰(P<0.01,q=5.63,q=6.21);治疗组TNF-α水平与对照组相比,第4周时也增加明显,但是与照射组相比明显下降(P<0.01,q=4.97q=7.42)。结论大鼠放射性肺损伤时TNF-α水平明显升高,在放射性肺损伤发展中起到重要作用,益赛普能显著降低它们的水平,并抑制炎症反应严重程度,从而能有效地防治放射性肺损伤。

Objective To observe the effect of recombinant human tumor necrosis factor-O receptor（rhTNFR：Fc）on tumor necrosis factor（TNF-α）and interleukin-6（IL-6）in radiation-induced lung injury,thus to find out a novel therapeutic strategy.Methods Seventy-two female SD rats were divided into 3 groups：control group,irradiation group and treatment group administered with rhTNFR：Fc.Rats in the irradiation group and treatment group were irradiated with linear accelerator at a single dose of 25 Gy.After irradiation rats in the treatment group were intraperitoneal injected with rhTNFR：Fc at a dose of 5 mg·kg-1 twice in the first week while rats in the control group and irradiation group were injected with the same volume of saline.Rats were killed in the 1,4,8 and 24 weeks.Samples of lung tissues were observed by using HE staining.Expression of TNF-α in lung was determined by immunohistochemistry while TNF-α in serum was determined by ELISA.Data were analyzed by SPSS software.Results Expressions of TNF-α in lung and serum increased significantly after irradiated in the irradiation group compared with the control group and reached the peak in the 4 weeks（P〈0.01,q=5.63,q=6.21）;Though expressions of TNF-α in the treatment group also increased compared with the control group,the difference between the irradiation group and treatment group was statistic significantly（P〈0.01,q=4.97,q=7.42）.Conclusion TNF-α plays an important role in radiation-induced lung injury.RhTNFR：Fc could suppress the inflammatory response and radiation-induced lung injury effectively by decreasing the levels of TNF-α.