Protective effect of pioglitazone in rat models of radiation-induced heart injury / 中国组织工程研究

ABSTRACT

BACKGROUND:There are many positive effects by activation of peroxisome proliferator activated receptor-gamma (PPARγ) signal pathway in cardiovascular system. Angiotensin II is closely related with myocardial fibrosis, however, there are few articles demonstrating that the activation of PPARγsignal pathway can weaken the expression of angiotensin II to improve the radiation-induced heart injury. OBJECTIVE:To evaluate the effect of angiotensin II type 1 receptor in the rat model of radiation-induced heart injury after PPARγsignal pathway is activated. METHODS:Sixty rats were randomly and equal y divided into five groupscontrol, pioglitazone, model, radiation+low-dose pioglitazone, radiation+high-dose pioglitazone. In the model, radiation+low-dose pioglitazone, radiation+high-dose pioglitazone groups, rats received 6 MV high energy X-ray irradiation at the range of 1.5 cm × 1.5 cm and the irradiation dose of 300 cGy/min, for 6 hours. Furthermore, rats in the radiation+low-dose pioglitazone and radiation+high-dose pioglitazone groups were given 10 and 20 mg/kg pioglitazone by lavage, for 30 days;rats in the model group were given 2 mL distil ed water. In the pioglitazone group, rats were treated with 10 mg/kg pioglitazone by lavage. RESULTS AND CONCLUSION:After rats were treated with pioglitazone, the heart injury and the heart fibrosis in the irradiated rats were decreased. The expressions of angiotensin II type 1 receptor mRNA and protein in the heart tissue were down-regulated. Experimental findings indicate that, pioglitazone intervention downregulates the expression of angiotensin II type 1 receptor in the rat models of radiation-induced heart injury and activation of PPARγsignal pathway al eviates the radiation-induced heart injury.