雌激素受体β对心肌梗死小鼠的保护作用及其机制-东南大学学报医学版

雌激素受体β对心肌梗死小鼠的保护作用及其机制

单位：河南大学淮河医院心内科, 河南开封 475000

分类号：R-33;R542.22

出版年·卷·期（页码）：2017·36·第三期（373-378）

摘要：

目的：探讨雌激素受体β（ERβ）对心肌梗死小鼠的保护作用及其机制。方法：取ERβ转基因小鼠（设为Tg-ERβ组）、非转基因的同窝对照野生型C57小鼠（NLC组）、Tg-ERβ转基因心肌梗死小鼠（Tg-ERβ+CAL组）和非转基因的同窝对照野生型C57心肌梗死小鼠（NLC+CAL组），于术后1、3和7 d超声心动图观察小鼠心脏结构和功能；RT-PCR检测小鼠心脏Ⅰ型胶原蛋白、α平滑肌肌动蛋白（α-SMA）和转化生长因子-β（TGF-β） mRNA；Masson染色检测心脏纤维化。结果：与NLC组相比，NLC+CAL组的舒张期左心室后壁厚度（PWTS）、收缩末期左心室前壁厚度（AWTD）、舒张期左心室前壁厚度（AWTS）、射血分数（EF）和短轴缩短率（FS）降低（P<0.05），收缩期左室内径（LVESD），Ⅰ型胶原蛋白、α-SMA和TGF-β增高（P<0.05）；与Tg-ERβ组相比，Tg-ERβ+CAL组的AWTD降低，EF、FS、Ⅰ型胶原蛋白、α-SMA和TGF-β增加（P<0.05）；与NLC组相比，Tg-ERβ组的LVESD和舒张期左室内径（LVEDD）增高（P<0.05），EF和FS降低（P<0.05）；与NLC+CAL组比，Tg-ERβ+CAL组的EF和FS增高（P<0.05），Ⅰ型胶原蛋白mRNA、α-SMA mRNA和TGF-βmRNA明显降低（P<0.05）；与Tg-ERβ+CAL组比，NLC+CAL组小鼠心脏冠脉以及心肌间质胶原纤维面积明显增加（P<0.05）。结论：心肌细胞限制性过表达ERβ可通过抑制心脏重塑、心肌纤维化或瘢痕化起到保护梗死心肌的作用。

Objective:To explore the protective effect and mechanism of estrogen receptor β(ERβ)on myocardial infarction mice. Methods:The transgenic ERβ mice(Tg-ERβ group), non-transgenic wild-type C57 mice(NLC group), Tg-ERβ transgenic myocardial infarction mice(Tg-ERβ+CAL)and NLC myocardial infarction mice(NLC+CAL group)were collected into our study. The cardiac structure and function were assessed by echocardiography 1 day, 3 days and 7 days after operation of myocardial infarction. RT-PCR was used to determine the type Ⅰ collagen mRNA, alpha smooth muscle actin(α-SMA)mRNA and transforming growth factor-β(TGF-β)mRNA and Masson staining was employed to detect the cardiac fibrosis. Results:Compared with the NLC group, the PWTS, AWTD, AWTS, EF and FS had decreased(P<0.05), while the VESD, type Ⅰ collagen, α-SMA and TGF-β had increased(P<0.05)in the NLC+CAL group. Compared with the Tg-ERβ group, AWTD had decreased(P<0.05),but the EF, FS, type Ⅰ collagen, α-SMA and TGF-β had increased(P<0.05)in the Tg-ERβ+CAL group. Compared with the NLC group, LVESD and LVEDD had increased(P<0.05),and the EF and FS had decreased(P<0.05)in the Tg-ERβgroup. Compared with NLC+CAL group, EF and FS had increased(P<0.05), type Ⅰ collagen, but the α-SMA and TGF-β had decreased(P<0.05)in the Tg-ERβ+CAL group. Compared with Tg-ERβ+ CAL group, the area of interstitial collagen fibers in the coronary artery and myocardial interstitium was increased(P<0.05)in the NLC+CAL group. Conclusion:Restricted overexpression of ERβ in cardiomyocytes can protect the myocardium by inhibiting cardiac remodeling and myocardial fibrosis or scarring.

参考文献：

[1] 唐小勇,钟万芬.D-二聚体水平评价急性心肌梗死危险程度及对预后的预测[J].现代医学,2016,44(5):697-701.
[2] 姚晶,侯静波.急性ST段抬高型心肌梗死非罪犯血管处理策略的研究进展[J].现代医学,2016,44(3):438-441.
[3] CHO J S 1,YOUN H J 1,HER S H,et al.The prognostic value of the left ventricular ejection fraction is dependent upon the severity of mitral regurgitation in patients with acute myocardial infarction[J].J Korean Med Sci,2015,30(7):903-910.
[4] OMOTO Y,IWASE H.Clinical significance of estrogen receptor βin breast and prostate cancer from biological aspects[J].Cancer Sci,2015,106(4):337-343.
[5] PASTORE M B,JOBE S O,RAMADOSS J,et al.Estrogen receptor-α and estrogen receptor-β in the uterine vascular endothelium during pregnancy:functional implications for regulating uterine blood flow[J].Semin Reprod Med,2012,30(1):46-61.
[6] BASHEY R I,DONNELLY M,INSINGA F,et al.Growth properties and biochemical characterization of collagens synthesized by adult rat heart fibroblasts in culture[J].J Mol Cell Cardiol,2012,24(7):691-700.
[7] CARVER W,NAGPAL M L,NACHTIGAL M,et al.Collagen expression in mechanically stimulated cardiac fibroblasts[J].Cir Res,2012,69(1):116-122.
[8] ZHANG W,CHANCEY A L,TZENG H P,et al.The development of myocardial fibrosis in transgenic mice with targeted overexpression of tumor necrosis factor requires mast cell-fibroblast interactions[J].Circulation,2012,124(19):2106-2116.
[9] DUERRSCHMID C,CRAWFORD J R,REINEKE E,et al.TNF Receptor 1 Signaling is Critically Involved in Mediating Angiotensin-Ⅱ-induced Cardiac Fibrosis[J].J Mol Cell Cardiol,2013,57(4):59-67.
[10] BURNS K A,LI Y,ARAO Y,et al.Selective mutations in estrogen receptor alpha's D-domain alters nuclear translocation and non-ERE gene regulatory mechanisms[J].J Biol Chem,2011,286(14):12640-12649.
[11] PROSSNITZ E R,BARTON M.The G-protein-coupled estrogen receptor GPER in health and disease[J].Nat Rev Endocrinol,2011,7(8):715-726.
[12] FLEMING I.Molecular mechanisms underlying the activation of eNOS[J].Pflugers Arch,2010,459(6):793-806.
[13] HUTCHENS M P,FUJIYOSHI T,KOMERS R,et al.Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo[J].Am J Physiol Renal Physiol,2012,303(3):F377-F385.
[14] MEYER M R,PROSSNITZ E R,BARTON M.The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function[J].Vascul Pharmacol,2011,55(1-3):17-25.
[15] MURATA T,DIETRICH H H,XIANG C,et al.G protein-coupled estrogen receptor agonist improves cerebral microvascular function after hypoxia/reoxygenation injury in male and female rats[J].Stroke,2013,44(3):779-785.

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