硫化氢通过下调MMP-11和MMP-16改善高甲状腺素诱导的大鼠心肌纤维化  

Hydrogen sulfide attenuating myocardial fibrosis induced by high thyroid hormone through down-regulating the expressions of MMP-11 and MMP-16 in rat models

作　　者：刘盛权 李琳[1] 龙俊蓉 谭文婷[1] 唐芬[1] 刘茂军[1] 梁彪[1] 李子宁[1] 褚春 杨军[1] 

机构地区：[1]南华大学附属第一医院心内科,湖南衡阳421001 [2]南华大学附属第二医院药剂科

出　　处：《中国老年学杂志》2017年第20期4985-4987,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金(81270181;81202830)

摘　　要：目的观察硫化氢(H2S)对甲状腺激素诱导的甲状腺功能亢进大鼠心肌纤维化的影响。方法通过左旋甲状腺素溶液(L-Thy,250μg/ml)腹腔注射(10 ml·kg-1·d-1)4 w,建立甲状腺功能亢进大鼠模型。以硫氢化钠(Na HS)作为外源性H2S供体,随机将40只SD雄性大鼠等分为对照组(Control组)、模型组(L-Thy组)、H2S干预组(L-Thy+H2S组)和H2S对照组(H2S组),4 w后处死大鼠,取左室心肌组织行Masson染色观察心肌纤维化,测量胶原容积分数(CVF),Western印迹检测MMP-11、MMP-16、PKCα靶蛋白的表达。结果与Control组相比,L-Thy组心肌胶原纤维堆积明显增加,CVF增高(P<0.05),而与L-Thy组相比,L-Thy+H2S组纤维化得到明显改善,CVF降低(P<0.05);H2S组与Control组镜下改变类似,CVF无明显差异(P>0.05);与Control组相比,L-Thy组MMP-11、MMP-16表达有显著差异(P<0.05);与L-Thy组相比,L-Thy+H2S组MMP-11、MMP-16表达明显减低(P<0.05),H2S组与Control组上述蛋白表达水平无明显差异(P>0.05)。各组之间PKCα蛋白表达没有明显差异(P>0.05)。结论 H2S可改善甲状腺激素诱导的甲状腺功能亢进大鼠心肌纤维化,其机制可能与下调MMP-11、MMP-16表达有关,但与PKCα通路无关。Objective To observe the effects of Hydrogen sulfide（ H2S） on myocardial fibrosis in rat models of hyperthyroidism induced by high thyroid hormone. Methods The hyperthyroidism in rats were induced by intraperitoneal injection of the L-Thyroxine solution（ 250 μg/ml,10 ml·kg^-1·d^-1） for 28 days. Sodium hydrosulfide was taken as the exogenous donor of hydrogen sulfide.40 male SD mice were randomly divided into control,model,intervention of H2S（ L-Thyroxine ＋ H2S group） and control of H2S（ H2S group） groups. All the mice were killed after 4 weeks,then Masson staining was performed to observe the myocardial fibrosis and the collagen volume fraction（ CVF） was measured,the expression of MMP-11,MMP-16 and PKCα was detected by Western blot. Results Compared with control group,the myocardial fibrosis and CVF were obviously increased in the L-Thyroxine group（ P〈0.05）. Compared with L-Thyroxine group,the myocardial fibrosis and CVF were significantly decreased in L-Thyroxine ＋ H2S group（ P〈0.05）,and there was no difference between control and H2S groups（ P〉0.05）. Compared to control group,the expression of MMP-11 and MMP-16 were up-regulated in L-Thyroxine group（ P〈0.05）,while the expression of above target proteins were down-regulated obviously in L-Thyroxine＋H2S group（ P〈0.05）,there was still no difference between control group and H2S group（ P〉0.05）. Also,the expression of PKCα was similar in each group（ P〉0.05）.Conclusions The H2S may improve the rats myocardial fibrosis of hyperthyroidism induced by thyroid hormone through regulating the expression of protein of MMP-11,MMP-16 but has nothing to do with the pathway of PKCα.

关 键 词：甲状腺功能亢进 心肌纤维化 H2S MMP-11、MMP-16 PKCΑ 

分 类 号：R581.1[医药卫生—内分泌]