Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

Objective:To assess the effects of recombinant human endostatin (rh-ES) on radiation-induced myocardial fibrosis.Methods:Totally 40 SD rats were randomly divided into 4 groups, including A group as normal control, B group receiving rh-ES with a dosage of 6 mg·kg -1·d -1, in traperitoneal injection, for 14 consecutive days, C group with local heart irradiation delivered to the precordial region of rats in five fractions with a dose of 25 Gy, D group receiving rh-ES as the same as B group and local heart irradiation as C group. At 1 and 3 months after irradiation, five rats were killed under anesthesia. Mason staining was used to observe myocardial injury and fibrosis. Western blotting was used to detect the expression of TGF-β1, CTGF and COL-I in myocardium. Results:Masson staining showed that no obvious myocardial fibrosis was found in group B at 1 month and 3 months after irradiation, while collagen fibers were distributed in myocardium in groups C and D. One month after irradiation, the result of semi-quantitative analysis showed that the CVF in group A was (5.20 ±0.75)%, which was significantly lower than that in group C (10.12 ±2.17)% ( t=4.74、4.93, P<0.01) and the CVF in group D (10.32 ±1.36), and the CVF of group C was similar to that of group D ( P<0.01). Three months after irradiation, CVF in group C (13.17±2.67)% was still higher than that in group A (5.23 ±1.32)% ( t=4.49, P<0.01), but lower than that in group D (16.92 ±3.58)% ( t=3.19, P<0.05). One month after irradiation, the expression of TGF-β1 in group A was 0.441 ±0.063, lower than that in group C (0.817 ±0.079, t=5.81, P<0.01). Three months after irradiation, the expression of TGF-β1 in group A was 0.501 ±0.110, lower than that in group C (0.832 ±0.150, t=4.19, P<0.01), and the expression of TGF-β1 in group D was 1.403 ±0.133, which was significantly higher than that in group C ( t=7.24, P<0.01). Conclusions:Radiation can cause the formation of myocardial fibrosis, and recombinant human endostatin may aggravate the formation of late radiation fibrosis.