沉默信息调节因子相关酶3在自发性高血压大鼠心肌高表达与左心室肥厚相关

目的观察沉默信息调节因子相关酶3(sirtuin3)在自发性高血压大鼠(SHR)心肌中的表达,并探讨sirtuin3在高血压所致左心室肥厚(LVH)中的作用。方法 24只29周龄SHR随机分为SHR30周龄组(喂养1周,n=11)和SHR38周龄组(喂养9周,n=13),另选20只29周龄Wistar-Kyoto(WKY)大鼠随机分为WKY30周龄组(喂养1周,n=10)和WKY38周龄组(喂养9周,n=10)作为正常对照。各组测定尾动脉收缩压和左心室质量(LVM)/体质量。Masson染色法分析左心室肌间质纤维化程度,心脏超声测定心功能。采用免疫组化,Western-blot及实时荧光定量PCR来检测心肌组织中sirtuin3的蛋白及mRNA表达。结果与WKY30、38周龄组大鼠比较,SHR30、38周龄组的收缩压30周龄(189.0±6.8)比(103.4±3.6)mmHg;38周龄(205.6±10.9)比(116.3±4.3)mmHg]、LVM/体质量30周龄(2.94±0.11)比(2.56±0.21);38周龄(3.21±0.15)比(2.68±0.24)]、左心室收缩末期内径30周龄(4.27±0.13)比(3.59±0.08)mm;38周龄(5.46±0.14)比(4.21±0.08)mm]、舒张末期室间隔厚度30周龄(2.63±0.15)比(2.09±0.06)mm;38周龄(2.82±0.09)比(2.35±0.08)mm]、舒张末期左心室后壁厚度30周龄(2.78±0.12)比(2.15±0.09)mm;38周龄(2.99±0.12)比(2.44±0.07)mm]、sirtuin3mRNA和蛋白表达升高(均P<0.05);左心室短轴缩短率、左心室舒张末期内径降低(均P<0.05),SHR大鼠表现出左心室明显肥厚,左心室收缩及舒张功能明显减低,并随着周龄的延长,心肌肥厚及心功能障碍加重(P<0.05)。结论心肌组织sirtuin3高表达与左心室肥厚密切相关。

Relationship between hyperexpression of sirtuin3 and left ventricular hypertrophy in spontaneously hypertensive rat

Objective To study the relationship between the overexpression of sirtuin3 and left ventricular hypertrophy (LVH) in myocardium of spontaneously hypertensive rats (SHR). Methods 29-week-old SHR (n=24) were randomly divided into two groups: 30-week-old SHR group (fed 1 week, n=11)and 38-week-old SHR group (fed 9 weeks, n=13). 29-week-old Wistar-Kyoto(WKY) rats (n=20) were used as controls and were randomly divided into 30-week-old WKY group (fed 1 week, n=10)and 38-week-old WKY group (fed 9 weeks, n=10). The systolic blood pressure (SBP) of tail artery and left ventricular mass/body mass (LVM/BM) were measured. Masson staining analysis was used to exam myocardial interstitial fibrosis of the left ventricular and cardiac ultrasound to measure the cardiac function. Real-time quantitative PCR, immunohistochemistry, and western blotting were used to detect the mRNA and protein expression of sirtuin3. Results Compared to the respective control groups, 30 and 38-week-old SHR showed SBP 30-week(189.0±6.8)vs (103.4±3.6)mm Hg, 38-week (205.6±10.9)vs (116.3±4.3)mm Hg], LVM/BM 30-week (2.94±0.11)vs(2.56±0.21); 38-week(3.21±0.15) vs(2.68±0.24)], left ventricular end systolic diameter30-week(4.27±0.13) vs(3.59±0.08)mm, 38-week:(5.46±0.14)vs(4.21±0.08)mm], end-diastolic interventricular septum depth 30-week(2.63±0.15) vs (2.09±0.06)mm; 38-week(2.82±0.09) vs (2.35±0.08)mm], end-diastolic left ventricular posterior wall depth 30-week(2.78±0.12) vs (2.15±0.09)mm; 38-week(2.99±0.12) vs (2.44±0.07)mm], as well as sirtuin3 mRNA and protein levels were all significantly increased(all P<0.05) while the fractional shortening and end-diastolic dimension of left ventricular were significantly decreased(all P<0.05). The SHR showed significant left ventricular hypertrophy and left ventricular dysfunction, which aggravated with time. Conclusion Overexpression of sirtuin3 in myocardium is closely related to the left ventricular hypertrophy.