Abstract:
Objective To investigate the expression of nitric oxide(NO), inflammatory mediators(TNF-a, IL-6) in serum and nitric oxide synthase(NOS) protein in aortic endothelial cells of rats with hypothyroidism induced by radioactive 131I, in order to find a safe dose of 131I for the prevention of hypothyroidism heart disease.
Methods Forty-five male rats were selected. The hypothyroidism model was established by intraperitoneal injection of 2.775, 5.550, 11.100, 16.650 MBq 131I + 0.5 mL saline into 36 male rats, with 9 rats in each group. The remaining 9 rats were taken as normal control group and only 0.5 mL saline was injected to each rat. Three rats were sacrificed in each group at 4, 8, and 16 weeks after 131I administration. The serum levels of IL-6, TNF-α and the aortal content of total-NOS activity were determined with chemiluminescence immunoassay. Western blotting was used to analyze the expression of rat aortic specimens of eNOS, nNOS, and iNOS, and count data were analyzed by the t test. A value of P<0.05 was considered statistically significant.
Results The serum levels of FT3, FT4 and TSH showed that all the groups of hypothyroidism model of rats were successfully constructed except 2.775 MBq group, and 5.550 MBq was regarded as an optimum dosage. The serum level of NO in rats(5.550 MBq) at 4 week increased to 24.01 mol/L and then reduced gradually; the level of serum IL-6 in 4, 8, and 16 were 209.23, 291.87, and 302.97 pg/mL, respectively. Compared with nomal control, statistical differences were observed at 8 and 16 week(t=8.841, 14.224, both P<0.05). The levels of TNF- alpha were 1441.23, 1601.85, and 1521.51 pg/mL, respectively, with statistical differences at different time points(t=21.021, 17.578, 14.498, all P<0.05). The expression of aortic endothelial NOS(eNOS) at different time points was 25 985, 16 306, and 6248. Compared with nomal control, the levels of protein in each group decreased, no statistical significance was observed at 4 week(t=3.546, P>0.05) and statistical differences were observed at 8 and 16 week(t=8.841, 14.224, both P<0.05). The expression of NOS(nNOS) was 24 562, 36 114 and 58 211, down at 4 week(t=3.546, P>0.05), and gradually increased at 8 and 16 week(t=5.751, 7.251, both P>0.05). The expression of inducible nitric oxide synthase(iNOS) was 55 973, 50 575 and 62 364, and all groups increased statistically(t=21.017, 16.412, 24.981, all P<0.05).
Conclusion The hypothyroidism induced by 131I has certain effect on the heart, and our study can provide a new idea for prevention of hypothyroid heart disease for clinical practice and reduction of cardiovascular disease.