雌二醇对血管紧张素Ⅱ诱导的高血压心肌肥厚小鼠T淋巴细胞的影响
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国家自然科学基金(81270428?81300999)


Effects of estradiol on T lymphocytes in angiotensin II-induced hypertrophy in mice
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    摘要:

    目的:研究雌二醇(estradiol,E2)对血管紧张素Ⅱ (angiotensinⅡ,AngⅡ)诱导的心肌肥厚小鼠T淋巴细胞的影响。方法:C57BL/6小鼠行卵巢切除术后被随机分为实验组(E2+AngⅡ)和对照组(Placebo+AngⅡ)。首先,实验组植入E2缓释片(0.25 mg/60 d),同时对照组植入对照剂。4周后两组均植入含有AngⅡ[1 000 ng/(kg-min),4 周]的渗透压泵诱导心肌肥厚。实验期间,分别在0-2-4-6-8周末测量小鼠血压,在4-8周末超声心动图测量小鼠舒张期室间隔厚度-左室内径-左室后壁厚度,计算射血分数(%EF)及短轴分数(%FS)。流式细胞技术分析T淋巴细胞变化。8周末通过HE染色观察心脏病理改变。结果:E2+AngⅡ组6-8周末血压水平及8周末心室舒张期室间隔厚度-左室后壁厚度均显著低于Placebo+AngⅡ组(P < 0.05)。给予AngⅡ前,两组总T淋巴细胞-CD4+T淋巴细胞-CD8+T淋巴细胞百分比及CD4+/CD8+比值均无统计学差异。给予AngⅡ 4周后,组间比较显示E2+AngⅡ组总T淋巴细胞百分比-CD8+T淋巴细胞百分比均显著低于Placebo+AngⅡ组(P < 0.05),CD4+T淋巴细胞百分比及CD4+/CD8+比值均显著高于Placebo+AngⅡ组(P < 0.05)。结论:E2能够改善长期AngⅡ灌注所致的心肌肥厚。在AngⅡ诱导心肌肥厚的过程中,E2能够导致总T淋巴细胞百分比-CD8+T淋巴细胞百分比显著降低,CD4+T淋巴细胞百分比及CD4+/CD8+比值显著升高。由此可见E2可能通过影响T淋巴细胞减轻AngⅡ所致的心肌肥厚。

    Abstract:

    Objective:To investigate effects of estradiol(E2) on T lymphocytes in angiotensinⅡ (AngⅡ)-induced hypertrophy in mice. Methods:Eight-to 10-week-old female C57BL/6 mice suffered ovariectomy were randomly divided into experiment group (E2+AngⅡ) and control group(Placebo+AngⅡ). At the beginning,E2 sustained release tablets (0.25 mg/60 d) were implanted into the experiment group and placebos were implanted into the control group. Four weeks after E2/placebo implantation,Osmotic mini-pumps containing AngⅡ [1000 ng/(kg-min),4 weeks] were implanted subcutaneously in both groups and induced hypertrophy. During the whole experiment,blood pressure was measured at the end of 1th,2th,4th,6th,8th week. At the end of 4th and 8th week,echocardiography was performed to measure interventricular septum (IVS),left ventricular interior diameter (LVID),left ventricular posterior wall (LVPW) at diastole and calculate ejection fraction (%EF) and fractional shortening (%FS). At the same time,we analyzed immunologic markers on T cells from mice in groups by multicolor flow cytometry (Canto Ⅱ,BD). Heart morphologic changes were detected by HE staining at the end of 8th week. Results:Blood pressure in E2+AngⅡ group was lower than that in Placebo+AngⅡ group at the end of 6th,8th week (P < 0.05). IVS and LVPW were alleviated in E2+AngⅡgroup than that in Placebo+AngⅡgroup. Before giving Ang II,the fraction of total T lymphocytes,CD4+T cells,CD8+T cells and the ratio of CD4+ and CD8+ were not statistically significant. Giving AngII for 4 weeks,the fraction of circulating total T lymphocytes cells and CD8+T cells in E2+AngⅡ group were lower than that in Placebo+AngII group (P < 0.05). The fraction of circulating CD4+T cells and the ratio of CD4+ and CD8+ in E2+AngⅡ group were higher than those in Placebo+AngII group (P < 0.05). Conclusion:E2 alleviated hypertrophy induced by chronic AngⅡ. During the process of hypertrophy,E2 could decrease the fraction of total T lymphocytes cells and CD8+T cells,and increase the fraction of CD4+T cells and the ratio of CD4+ and CD8+. Our research indicated that E2 could affect T cells population to alleviated hypertrophy induced by AngⅡ.

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蔡诗昆,刘正霞,周 萍,刘 莹,鲁 翔.雌二醇对血管紧张素Ⅱ诱导的高血压心肌肥厚小鼠T淋巴细胞的影响[J].南京医科大学学报(自然科学版),2015,(2):149-154

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  • 收稿日期:2014-08-13
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  • 在线发布日期: 2015-02-13
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