中国呼吸与危重监护杂志

中国呼吸与危重监护杂志

甲磺酸伊马替尼对放射性肺炎小鼠肺部氧化应激指标及转化生长因子-β1 表达影响的研究

查看全文

目的 探讨甲磺酸伊马替尼对放射性肺炎小鼠肺部氧化应激指标及转化生长因子-β1(TGF-β1)表达的影响。 方法 将 45 只清洁级 C57BL/6 小鼠随机平均分为空白组、治疗组和模型组。每天给予治疗组与模型组胸部照射,照射结束 4 h 后给予治疗组小鼠甲磺酸伊马替尼(给药剂量 0.081 g/kg);其余组仅给予生理盐水。实验 30 d 后,将各组小鼠处死,取其左右肺,分别采用 HE 染色及免疫组化观察其病理变化及肺部 TGF-β1 的表达情况。制作肺匀浆,检测其中谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)、总抗氧化能力(T-Aoc)及超氧化物歧化酶(SOD)等氧化应激指标含量。 结果 治疗组 GSH-PX、T-Aoc 及 SOD 分别为(173.15±12.21)U、(119.33±11.06)U/mgprot 及(1.73±0.33)U/mgprot,均明显高于模型组(P 均<0.05),而 MDA 含量则为(0.68±0.08)nmol/mgprot,明显低于模型组(P<0.05)。HE 染色及免疫组化结果显示,治疗组仅出现轻度肺泡炎改变及部分 TGF-β1 阳性表达,模型组则多为中级以上肺泡炎及高水平 TGF-β1 阳性表达,治疗组 HE 染色及免疫组化评分分别为(1.26±0.12)分和(0.31±0.12)分,均明显低于模型组(P<0.05)。 结论 甲磺酸伊马替尼可有效改善放射性肺炎小鼠肺部氧化应激紊乱,抑制小鼠肺部 TGF-β1 的表达,值得开展深入研究。

Objective To investigate the effect of imatinib mesylate on radiation-induced lung injury mice and its influence on the oxidative stress and transforming growth factor-β1 (TGF-β1) expression in mice. Methods Forty-five C57BL/6 mice were divided into a treatment group, a control group and a model group. The treatment group and model group were given radiation of 18 Gy delivered in the thorax. After 4 h daily of the radiation, the treatment group received imatinib mesylate of 0.081 g/kg, while the other groups were given normal saline solution. The experiments were continued for 30 days. After the experiments, the lungs of mice were divided into 4 parts. The haematoxylin and eosin and immunohistochemical stain were prepared to observe the situation of pathology and TGF-β1. The lung homogenate was prepared and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant capacity (T-Aoc) and glutathione peroxidase (GSH-PX) were detected. Results The levels of GSH-PX, T-Aoc and SOD were (173.15±12.21) U, (119.33±11.06) U/mgprot and (1.73±0.33) nmol/mgprot in the treatment group, significantly higher than the control group, while the levels of MDA was (0.68±0.08) nmol/mgprot, significantly lower than the control group (P<0.05). The HE and immunohistochemical stain showed that there were mild alveolar inflammatory changes in the treatment group while such changes were serious in the model group. The scores of HE and immunohistochemical were 1.26±0.12 and 0.31±0.12 in the treatment group, significantly lower than those in the control group (P<0.05). Conclusion The imatinib mesylate can effectively ameliorate the oxidative stress and inhibite TGF-β1 expression in radiation-induced lung injury mice.

关键词: 甲磺酸伊马替尼; 放射性肺炎; 转化生长因子-β1

Key words: Imatinib mesylate; Radiation-induced lung injury; Transforming growth factor-β 1

引用本文: 刘文秀, 杨娟, 曹博, 高院. 甲磺酸伊马替尼对放射性肺炎小鼠肺部氧化应激指标及转化生长因子-β1 表达影响的研究. 中国呼吸与危重监护杂志, 2017, 16(5): 446-450. doi: 10.7507/1671-6205.201703027 复制

登录后 ,请手动点击刷新查看全文内容。 没有账号,
登录后 ,请手动点击刷新查看图表内容。 没有账号,
1. 黎建绪, 郑雅梅, 胡晓燕, 等. 艾迪注射液对小鼠放射性肺损伤的防治作用. 医药导报, 2014, 33(2): 184-188.0
2. Li X, Xu G, Qiao T, et al. Effects of CpG oligodeoxynucleotide 1826 on acute radiation-induced lung injury in mice. Biol Res. 2016, 49(1): 8.
3. Son Y, Lee HJ, Rho JK, et al. The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer. BMC Pulm Med. 2015, 15: 68.
4. Fang XM, Hu CH, Hu XY, et al. An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray. Chin Med J (Engl). 2015, 128(12): 1636-1642.
5. Malaviya R, Gow AJ, Francis M, et al. Radiation-induced lung injury and inflammation in mice: role of inducible nitric oxide synthase and surfactant protein D. Toxicol Sci. 2015, 144(1): 27-38.
6. Elias MH, Bada AA, Azlan H, et al. BCR-ABL kinase domain mutations, including 2 novel mutations inimatinib resistant Malaysian chronic myeloid leukemia patients-Frequency and clinical Outcome. Leuk Res, 2014, 38(4): 454-459.
7. Mathisen MS, Kantarjian HM, Cortes J, et al. Practical issues surrounding the explosion of tyrosine kinase inhibitors for the management of chronic myeloid leukemia. Blood Rev, 2014, 28(5): 179-187.
8. 孙敬方. 动物实验方法学. 北京: 人民卫生出版社, 2001, 198-201.
9. Jiao J, Gai QY, Zhang L, et al. High-speed homogenization coupled with microwave-assisted extraction followed by liquid chromatography-tandem mass spectrometry for the direct determination of alkaloids and flavonoids in fresh Isatis tinctoria L. hairy root cultures. Anal Bioanal Chem. 2015, 407(16): 4841-4848.
10. Carter CL, Jones JW, Barrow K, et al. A MALDI-MSI Approach to the Characterization of Radiation-Induced Lung Injury and Medical Countermeasure Development.Health Phys. 2015, 109(5): 466-478.
11. Giridhar P, Mallick S, Rath GK, et al. Radiation induced lung injury: prediction, assessment and management. Asian Pac J Cancer Prev. 2015, 16(7): 2613-2617.
12. Santyr G, Fox M, Thind K, et al. Anatomical, functional and metabolic imaging of radiation-induced lung injury using hyperpolarized MRI. NMR Biomed. 2014, 27(12): 1515-1524.
13. Murigi FN, Mohindra P, Hung C, et al. Dose Optimization Study of AEOL 10150 as a Mitigator of Radiation-Induced Lung Injury in CBA/J Mice. Radiat Res. 2015, 184(4): 422-432. doi: 10.1667/RR14110.1.
14. Huang Y, Liu W, Liu H, et al. Grape seed pro-anthocyanidins ameliorates radiation-induced lung injury. J Cell Mol Med. 2014, 18(7): 1267-1277.
15. Zhang J, Li B, Ding X, et al. Genetic variants in inducible nitric oxide synthase gene are associated with the risk of radiation-induced lung injury in lung cancer patients receiving definitive thoracic radiation. Radiother Oncol. 2014, 111(2): 194-198.
16. Yu J, Yuan X, Liu Y, et al. Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice. Lung. 2016, 194(1): 67-74.
17. Zhao DY, Qu HJ, Guo JM, et al. Protective Effects of Myrtol Standardized Against Radiation-Induced Lung Injury. Cell Physiol Biochem. 2016, 38(2): 619-634.
18. Kralj E, Zakelj S, Trontelj J, et al. Absorption and elimiation of imatinib through the rat intestine in vitro. Int J Pharm, 2014, 460(1/2): 144-149.
19. Quinta’s-Cardama A, Jabbour EJ. Considerations for early switch to nilotinib or dasatinib in patients with chronic myeloid leukemia with inadequate response to first-line imatinib. Leuk Res, 2013, 37(5): 487-495.
20. Liu Y, Tan D, Tong C, et al. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway. Chem Biol Interact. 2015, 242:363-371.