目的通过研究左旋甲状腺素(LT4)、维生素E(VitE)及二者联合治疗对甲状腺功能减退(甲减)大鼠氧化应激及心肌细胞凋亡的影响,进一步探讨甲减心肌损伤的发生机制及其治疗方法。方法将sD雄性大鼠分为正常对照组、丙基硫氧嘧啶组(PTU)、LT4治疗组(PTU+LT4)、VitE治疗组(PTU+VitE)、LT4和VitE联合治疗组(PTU+LT4+VitE)。测定血清T3、T4、TSH水平以及血清、心肌组织超氧化物歧化酶(SOD)活性和丙二醛含量;用TUNEL法检测心肌细胞凋亡指数。结果(1)与正常对照组比较,PTU组、PTU+VitE组T3、T4水平明显降低,TSH显著升高(P〈0.05);与PTU组比较,PTU+LT4组、PTU+LT4+VitE组T3.T4水平明显升高,TSH显著降低(P〈0.05);PTU组与PTU+VitE组L、T4、TSH水平差异无统计学意义(P〉0.05)。(2)与正常对照组比较,PTU组血清及心肌组织丙二醛含量显著升高(P〈0.05),其他各组之间差异无统计学意义(P〉0.05);与正常对照组比较,PTU组血清SOD活性显著降低(P〈0.05),但心肌组织SOD活性各组之间差异无统计学意义(P〉0.05)。(3)与正常对照组比较,PTU组、PTU+VitE组心肌细胞凋亡显著升高(P〈0.05);与PTU组比较PTU+LT4组、PTU+LL+VitE组凋亡显著降低(P〈0.05)。结论LT4、VitE及二者联合治疗可降低甲减大鼠心肌细胞凋亡,其机制可能与甲状腺功能改善和氧化应激水平降低有关。
Objective To investigate the oxidative stress status and cardiac myocyte apoptosis in rats with propyhhiouracil-induced hypothyroidism and to examine the effect of levothyroxine ( LT4 ), vitamin E ( VitE ), and both supplementation on this experimental model. Methods Male Sprague Dawley rats were divided into normal control group(NC) , propyhhiouracil group(PTU) , LT4 treatment group( PTU + LT4 ) , VitE treatment group ( PTU + VitE), LT4 and VitE combination therapy group (PTU + LT4 + VitE). Serum T3, T4, TSH levels, serum and myocardial superoxide dismutase ( SOD ) activity and malondialdehyde (MDA) content were determined. Cardiac myocyte apoptotic index was made with TUNEL. Results ( 1 ) Compared with NC group, T3 and T4 levels were significantly lower and TSH level was significantly higher in PTU group and PTU+VitE groups( P〈0.05 ). Compared with PTU group, T3 and T4 levels were significantly higher and TSH level was significantly lower in PTU + LT4 group and PTU + LT4 + VitE group( P〈0.05 ). There were no statistical differences in T3 , T4 , and TSH levels between PTU group and PTU + VitE group ( P〉0.05 ). (2) Compared to NC group, serum and myocardial MDA levels in PTU group increased significantly (P〈 0.05 ), serum SOD activity decreased significantly ( P 〈 0.05 ) , while myocardial SOD activity showed no significant difference(P〉0.05 ). ( 3 ) Compared with NC group, myocardial apoptosis index was significantly higher in PTU and PTU + VitE groups( P〈0.05 ). Compared with PTU group, myocardial apoptosis index was significantly lower in PTU + LT4 group and PTU + LT4 + VitE group ( P〈0.05 ). Conelusion LT4, VitE, and their combined treatment of hypothyroidism in rats reduce the myocardial cells apoptosis, which may be related to the improvement of thyroid function and amelioration of oxidative stress.