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目的研究替米沙坦对大鼠放射性肺损伤的保护作用,并探讨其机制。方法将100只大鼠随机等分成5组,分别为空白对照组(生理盐水)、阳性对照组[放疗+10 mg/(kg·d)泼尼松]、模型组(放疗+生理盐水)、替米沙坦低剂量组[放疗+8 mg/(kg·d)替米沙坦]、替米沙坦高剂量组[放疗+16 mg/(kg·d)替米沙坦]。观察大鼠的活动及体重变化情况,并于照射后3 d、7 d、14 d、28 d解剖,记录肺湿重、进行HE染色及Masson染色观察肺组织的炎症及纤维化情况,采用免疫印迹法检测TGF-β及smad2的表达情况,通过Elisa试剂盒检测IL-2、IL-6含量;并采用分子对接的方法进一步验证替米沙坦改善放射性肺损伤的机制。结果替米沙坦给药组与模型组相比,第14天、28天时炎症及纤维化情况均减轻,大鼠的一般状态得到改善,替米沙坦下调了大鼠肺组织中TGF-β及smad2的表达量,降低了大鼠血清中IL-2及IL-6含量;分子对接结果显示,替米沙坦分子与TGF-β蛋白活性口袋中5个氨基酸存在分子间作用力,可形成稳定构象。结论替米沙坦对大鼠放射性肺损伤有保护作用,这种作用可能与其下调TGF-β及smad2的表达量,降低IL-2及IL-6的含量有关。
Objective To study the protective effect of telmisartan on radiation-induced lung injury in rats and its mechanism. Methods 100 rats were randomly divided into 5 groups: blank control group (normal saline), positive control group (radiation +10 mg / (kg · d) prednisone), model group (radiotherapy + saline) Telmisartan low dose group [radiotherapy + 8 mg / (kg · d) telmisartan], telmisartan high dose group [radiotherapy + telmisartan +16 mg / (kg · d)]. The changes of rat activity and body weight were observed. After 3 d, 7 d, 14 d and 28 d of irradiation, the wet weight of the lungs were dissected and the lung tissues were infiltrated and stained with HE staining and Masson staining. The expression of TGF-β and smad2 was detected by Western blotting. The contents of IL-2 and IL-6 were detected by Elisa kit. Molecular docking was used to further verify the mechanism of telmisartan in improving radiation-induced lung injury. Results In telmisartan group, inflammation and fibrosis were relieved on the 14th and 28th days compared with the model group, and the general state of the rats was improved. Telmisartan down-regulated the expression of TGF-β And smad2 expression in rat serum decreased the content of IL-2 and IL-6 in rat serum. The results of molecular docking showed that there were intermolecular forces between telmisartan and 5 amino acids in the active pocket of TGF- Stable conformation. Conclusion Telmisartan has a protective effect on radiation-induced lung injury in rats, which may be related to down-regulating the expression of TGF-β and smad2 and decreasing the content of IL-2 and IL-6.