硫化氢下调STAT3改善MMPs/TIMPs失调及高甲状腺素诱导的心肌纤维化

Improvement of hydrogen sulfide on the disorder of MMPs/TIMPs and myocardial fibrosis induced by high thyroxine through downregulating STAT3

OBJECTIVE To observe the effects of exogenous hydrogen sulfide (H₂S) on myocardial fibrosis induced by high dose thyroxine and the expression of MMPs/TIMPs and STAT3. METHODS Forty male SD rats were divided into four groups by a completely randomized method:control group (Con), hyperthyroidism group (L-Thy), hydrogen sulfide intervention group (L-Thy + H₂S) and hydrogen sulfide control group (H₂S). A rat model of hyperthyroidism was established by intraperitoneal injection of levothyrocine (L-Thy,10 mL·kg^-1·d^-1). Then,animals in L-Thy + H₂S group and H₂S group were treated with sodium hydrosulfide solution (1 ml·kg^-1·d^-1),animals in Con group and L-Thy group were treated with the same volume of saline. These rats were sacrificed after four weeks, the collagen deposition of left ventricular myocardium was observed by Masson staining, the collagen volume fraction (CVF) was calculated, and the expressions of MMP8, MMP16, TIMP1 and STAT3 proteins were detected by Western-blot. RESULTS Compared with Con group, the L-Thy group showed significantly increased collagen fibers, the CVF also had increased collagen fibers (P<0.05). Besides, the MMP8, MMP16 and STAT3 showed increased protein expression, while TIMP1 protein expression decreased significantly (P<0.05). Compared with L-Thy group, the deposition of collagen fibers in H2S+L-Thy group was improved, and CVF decreased (P<0.05). In addition, the expressions of MMP8, MMP16 and STAT3 proteins decreased, TIMP1 expression obviously increased (P<0.05). CONCLUSION Hydrogen sulfide may improve the expression disorder of MMPs/TIMPs by downregulating STAT3, thereby improving the high dose thyroxine induced myocardial fibrosis.