丹参对自发性高血压大鼠左室肥厚及心肌凋亡的影响

The Effect of Salvia miltiorrhiza Bge on Left Ventricular Hypertrophy and Myocardial Apoptosis in Spontaneous Hypertensive Rats

目的观察丹参对自发性高血压大鼠左室肥厚的作用及左室心肌组织细胞凋亡的影响,并探讨其作用机制。方法实验用WKY大鼠做阴性对照组,SHR大鼠分为对照组和治疗组。治疗组给予丹参注射液腹腔内注射12周,其余两组分别注射相当容积的蒸馏水。测量大鼠尾动脉收缩压(systolic b lood pressure,SBP)及左心室重量指数(left ventricu larm ass index,LVM I)。应用HE、VG染色、免疫组织化学的方法,结合计算机图像分析技术,检测心肌细胞的直径和面积、心肌组织胶原体积比例(collagen volum e fraction,CVF)、血管周围胶原面积和管腔面积比例(perivasu lar c ircum ferentiall area,PVCA),采用TdT介到的dUTP缺口末端标记技术(TUNEL)检测心肌细胞凋亡。结果与WKY大鼠相比,20周龄SHR大鼠的SBP、LVM I、心肌细胞的直径、面积、CVF、PVCA、心肌凋亡细胞数显著增加,用丹参治疗后,SHR除收缩压外余指标均显著性下降(P<0.05)。结论长期应用丹参治疗可预防和逆转高血压大鼠左室肥厚形成,其机制可能与丹参降低心肌细胞凋亡有关。

Objective To study the effect of Salvia miltiorrhiza Bge（SMB） on left ventricular hypertrophy（ LVH） and myocardial apoptosis in spontaneous hypertensive rats and to investigate its mechanism. Methods Normal Wistar-kyoto （WKY） rats were used as negative control, and spontaneous hypertensive rats（SHR） were randomly divided into two groups： either receiving placebo or Salvia miltiorrhiza Bge（SMB）. SMB （1 g/kg, d） was injected intraperitoneally for 12 weeks. Systolic blood pressure（SBP）and left ventricular mass index（LVMI）were measured. HE,VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size, diameter, the collagen volume fraction（CVF） and perivascular circumferential area（PVCA）. Cardiac apoptosis was evaluated by terminal deoxynucleotidy transferase mediated dUTP-biotin nick end labelling （TUNEL） assay. Results As compared with WKY rats, SBP,LVMI, cardiomyocyte size, diameter, CVF, PCVA and the density of TUNEL-positive cells increased markedly in the 20-week-old spontaneous hypertensive rats. SMB decreased LVMI（P〈0.01）, cardiomyocytes size （P 〈 0.01） ,collagen volume fraction （P〈 0.01） ,perivascular circumferential area （P〈0.01） ,TUNEL-positive cells （P〈 0.01）with no effect on SBP. Conclusion Chronic use of SMB can inhibit and regress the development of LVH in spontaneous hypertensive rats independent of BP. Myocardial apoptosis may be involved in the reversal mechanism of LVH by SMB.