乌司他丁对大鼠放射性肺损伤中TNF—α及IL-6的影响

Effect of ulinastatin on tumor necrosis factor and interleukin-6 in rats with radiation-induced lung injury

目的观察乌司他丁（天普洛安）对大鼠放射性肺损伤过程中TNF—α及IL-6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：健康对照组、单纯照射组和乌司他丁治疗组，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。照射组照射后通过尾静脉注射乌司他丁（100000U·kg^-1·d^-1），共计7d。对照组和照射组注射同等体积的生理盐水。于照射后2h、4、8和24周处死动物，取部分肺组织行HE染色及Masson染色，观察组织学变化，另提取组织蛋白用免疫印迹杂交方法检测肺组织中TNF-α水平，使用酶联免疫吸附分析法检测血清中IL-6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中TNF—α及血清中IL-6水平与对照组相比，明显升高，并在第4周时达到顶峰（q=5．63、6．21，P〈0．01）；治疗组TNF—α和IL-6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（q=4．97、7．42，P〈0．01）。结论大鼠放射性肺损伤时TNF—α及IL-6水平明显升高，在放射性肺损伤发展中起到重要作用，乌司他丁能显著降低其水平，并抑制炎性反应，从而能有效地防治放射性肺损伤。

Objective To observe the effect of ulinastatin on tumor necrosis factor （TNF-α） and interleukin-6（IL-6） in radiation-induced lung injury. Methods Seventy-two female SD rats were randomly divided into 3 groups as control group, irradiation group and treatment group （administered with Ulinastatin）. Rats in irradiation group and treatment group were irradiated with linear accelerator at a single dose of 25 Gy. After irradiation rats in treatment group were injected daily with ulinastatin at a dose of 100 000 U· kg^- 1· d ^-1 for 7 days through caudal vein while rats in control group and irradiation group were injected with the same volume of saline. Rats were killed at 2 h, 4, 8 and 24 weeks. Samples of lung tissues were observed by using HE staining. Expression of TNF-α in lung was determined by Western blot and expression of IL-6 in serum was determined by ELISA. Data were analyzed by SPSS software. Results Expressions of TNF-α in lung and IL-6 in serum increased significantly after irradiated in irradiation group compared with control group, and it reached the peak at 4 weeks（ q = 5.63,6.21, P 〈 0.01 ）. Though expressions of TNF-αand IL-6 in treatment group also increased compared with control group, the difference between irradiation group and treatment group was statistic significantly （ q = 4.97,7.42, P 〈 0.01 ）. Conclusions TNF-α and IL-6 play an important role in radiation- induced lung injury. Ulinastatin could suppress the inflammatory response and radiation-induced lung injury effectively by decreasing the levels of TNF-α and IL-6.