The protective effect of inhibiting CD47 expression on radiation-induced lung injury / 中华放射肿瘤学杂志

ABSTRACT

Objective:To study the protective anti-radiation effect of inhibiting CD47 expression in the lung tissues of mice and to explore the associated mechanism.Methods:Female C57BL/6 mice ( n = 60) were randomly divided into four groups normal, blank, negative and positive. The blank group received only whole-lung irradiation; The negative group received whole-lung irradiation and tracheal infusion of adeno-associated virus containing nonsense sequence shRNA; The positive group received whole lung irradiation and tracheal drip containing adeno-associated virus containing shRNA expression of CD47. Fresh blood samples were collected at 24 h, 4 weeks, and 12 weeks post-irradiation, respectively. The expression level of CD47 mRNA was determined by RT-PCR. Determination of hydroxyproline content by alkaline hydrolysis. The LC3 expression level was measured by immunohistochemical staining. Serum transforming growth factor-β 1 (TGF-β 1) and tumor necrosis factor-α (TNF-α) levels were assessed by ELISA. Results:RT-PCR showed that the relative expression level of CD47 mRNA in the lung tissues in the positive group was significantly lower compared to those in the negative group, the normal group, the blank group (24-hour, P were <0.001,<0.001,<0.001, respectively. 4-weeks, P were <0.001,0.003,0.001, respectively. 12-weeks, P were 0.009, 0.002, 0.005, respectively). There were no significant differences in CD47 mRNA expression in the three groups except the positive group (all P>0.05), and there was no significant difference in CD47 mRNA expression with time in each group (all P>0.05).The serum TGF-β1 content was higher in the 24 h, 4-week, and 12-week blank groups ( P were <0.001, 0.003 and 0.003, respectively) and negative groups( P were 0.001, 0.021 and 0.034, respectively) after irradiation than that in the mice in the normal group. At the same time, the serum TNF-α of positive group after irradiation (24 hours, 4 weeks, 12 weeks, P were 0.022, <0.001, <0.001, respectively) were significantly higher than those of the normal group. The content of hydroxyproline in the blank group was significantly higher than that in the normal group (4 weeks, 12 weeks, P were 0.002, <0.001, respectively). Immunohistochemical indications 24 h after irradiation was higher than the expression of LC3 in mouse lung tissue at 4 weeks and 12 weeks (all P < 0.001). The difference between the negative group and the blank group was not obvious ( P>0.05). Conclusions:Inhibition of CD47 expression can reduce the degree of radiation-induced pneumonia and pulmonary fibrosis probably via enhanced autophagy. CD47 may represent a novel target for the protection of radiation-induced lung injury.