Protective effect of pituitary adenylate cyclase-activating polypeptide 38 on acute radiation-induced myocardial injury

doi:10.3969/j.issn.1674-8115.2021.02.001

Abstract

Abstract: Objective

·To explore the effect of pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) on radiosensitivity of myocardial cells and its potential protective effect on acute radiation-induced myocardial injury.

Methods

·The radiation-related cardiac injury models were established by using 6 MV X-ray with H9C2 cardiomyocytes and male C57BL/6J mice which were pre-treated with different doses of PACAP38 prior to radiation exposure. H9C2 cells were treated with 10^-9 and 10^-7 mol/L PACAP38 2 h before irradiation. 10 μg of 0.1 μg/μL PACAP38 was administered to C57BL/6J mice intraperitoneally at 2 h before irradiation and additional doses were given at 24 h and 48 h after irradiation. In vivo and in vitro myocardial radiation injury models were divided into control group, PACAP38 group, irradiation group (IR) and PACAP38+IR group. The specific irradiation doses in vitro were 2, 4, 8 and 12 Gy. The specific irradiation dose in vivo were 14 Gy, one fraction irradiation. CCK-8 and clonogenesis assays were used to examine cell viability and radiosensitivity, respectively. Hematoxylin and eosin staining was used to evaluate the pathological changes of myocardial tissue in mice after one-month irradiation.

Results

·The cell viability of H9C2 cardiomyocytes pretreated with PACAP38 was significantly higher than that of irradiation (12 Gy) alone [10^-7mol/L PACAP38+IR group vs IR group, (98.63±2.70)% vs (83.67±0.78)%, P=0.000]. The survival fraction at 2 Gy increased from 0.53 to 0.63 and 0.70 after 10^-9 and 10^-7 mol/L PACAP38 pretreatment, and the sensitivity enhancement ratio of 10^-9 and 10^-7 mol/L PACAP38 pretreatment groups were 0.95 and 0.91, respectively. In vivo studies showed that PACAP38 could significantly alleviate the pathological damage of myocardial tissue after irradiation (14 Gy), including cardiomyocyte degeneration, eosinophilic enhancement, cytoplasmic vacuolation, nuclear pyknosis and myocardial fiber distortion.

Conclusion

·PACAP38 can significantly reduce the radiosensitivity of myocardial cells and has a certain protective effect on acute radiation-induced myocardial injury.

Key words: pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), irradiation model, radiation-induced myocardial injury, cardioprotectant

CLC Number:

R730

Huan LI, Pei-qiang YI, Jun SU, Pei-zhan CHEN, Cheng XU, Lu CAO, Jia-yi CHEN, Min LI. Protective effect of pituitary adenylate cyclase-activating polypeptide 38 on acute radiation-induced myocardial injury[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(2): 129-133.

Figures/Tables 4

Fig 1 Protective role of PACAP38 against IR-induced cytotoxicity in H9C2 cells

Fig 2 Effect of PACAP38 intervention on SF2 of H9C2 cells

Tab 1 Effect of PACAP38 on radiosensitivity of H9C2 cells (xˉ±s)

Group	D₀/Gy	D_q/Gy	SF2	SER
Control	1.59±0.01	1.27±0.07	0.53±0.02	1.00
PACAP38(10^-9 mol·L^-1)	1.67±0.03	1.70±0.06	0.63±0.01	0.95±0.02
PACAP38(10^-7 mol·L^-1)	1.76±0.06	1.99±0.11	0.70±0.02	0.91±0.03

Fig 3 Protective effect of PACAP38 treatment on myocardial tissue after irradiation（H-E staining, ×400）

TrendMD

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