Effects and mechanisms of exogenous hydrogen sulfide on inhibiting the activation of p38MAPK/NF-κB p65 pathway to improve diabetic myocardial fibrosis / 解放军医学杂志

ABSTRACT

Objective To study the effects of exogenous hydrogen sulfide (H2S) on myocardial fibrosis of diabetic mice and the mechanism thereof. Methods Twenty-four male adult C57BL/6J mice were randomly divided into 4 groups (6 each) normal control group (NC group), diabetes mellitus group (ALX group), diabetes mellitus treated with low dose NaHS group (ALX+LDNaHS group) and diabetes mellitus treated with high dose NaHS group (ALX+HDNaHS group). The diabetic mouse model was established by intraperitoneal injection of alloxan at 200mg/kg. Mice in NC group and ALX group drank tap water freely everyday, and in ALX+LDNaHS group and ALX+HDNaHS group were provided with sodium hydrosulfide (NaHS, donor of H2S, 30μmol/L and 90μmol/L, respectively) in drinking water, and the histological specimens of mice were examined 8 weeks later. The morphological changes of cardiac tissue were examined with HE staining. The expressions of mRNA of p38mitogen-activated protein kinase (p38MAPK) and nuclear transcription factor kappa B p65 (NF-κB p65) were detected by Real-time PCR, and the expressions of p-p38MAPK, p-NF-κB p65 and Collagen I proteins were detected by Western blotting. Results Compared with NC group, the expression of collagen increased and there was fibrillation in the myocardial matrix, the expressions of mRNA of p38MAPK and NF-κB p65 increased obviously (P<0.01), the protein expressions of p-p38MAPK, p-NF-κB p65 and Collagen I increased significantly (P<0.01) in ALX group; after intervention of H2S, the cardiac muscle fibers were parallel arranged, the expression of collagen was visibly decreased and there was less fibrillation in the myocardial matrix, the expressions of mRNA of p38MAPK and NF-κB p65 were obviously decreased (P<0.01), the protein expressions of p-p38MAPK, p-NF-κB p65 and Collagen I were significantly decreased (P<0.01), and more improvement was observed in ALX+HDNAHS group than in ALX+LDNAHS group (P<0.05). Conclusion H2S can ameliorate myocardial fibrosis in diabetic mice, which might be related to the regulation of p38MAPK and NF-κB p65-mediated inflammatory reaction.