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左旋甲状腺素和维生素E干预对甲状腺功能减退大鼠心肌氧化应激和细胞凋亡的影响

Effect of levothyroxine and vitamin E treatment on oxidative stress and myocardial apoptosis in rats with hypothyroidism

摘要:

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T3、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+ LT4+ 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.

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abstracts:

Objective To investigate the oxidative stress status and cardiac myocyte apoptosis in rats with propylthiouracil-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),propylthiouracil 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 ).Conclusion 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.

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