高血压对大鼠心肌间质重构的影响及药物干预研究

目的:观察神经内分泌型高血压大鼠心肌间质重构在药物干预下的变化,探讨高血压心肌间质重构机制及抑制方法.方法:建立神经内分泌型高血压大鼠动物模型,34只Wistar大鼠随机分为哌唑嗪组(Hα)、抑平舒组(Hace)、己酮可可碱(pentoxifylline,PTX)组(Hptx)和高血压对照组(Hc).10只正常Wistar大鼠作为正常对照组(Nc).观察各组大鼠血压、血清Ⅲ型前胶原、肿瘤坏死因子-α(TNF-α)水平及心肌胶原容积分数(collagen volume fraction, CVF)变化.结果:Hace组治疗后血压、左室质量、血清Ⅲ型前胶原和TNF-α水平、各项CVF均较Hc组明显降低(P < 0.05);Hα组治疗后血压、左室质量低于Hc组(P < 0.05),而Ⅲ型前胶原、TNF -α水平仍高于Nc组(P < 0.05); Hptx组较Hc组治疗后血压和左室质量无明显降低(P > 0.05),但血清Ⅲ型前胶原和TNF-α水平、各项CVF明显降低(P ＜ 0.05).结论:血管紧张素转换酶抑制剂(ACEI)逆转心肌纤维化的作用可能与抑制血管紧张素Ⅱ(AngⅡ)有关,PTX抑制和逆转心肌纤维化可能与拮抗TNF-α有关.

Effects of Hypertension and Pharmacological Intervention on the Left Ventricular Remodeling in Neuroendocrine Hypertensive Rats

Objective: To investigate the effect of medication on left ventricular myocardial matrix remodeling in neuroendocrine hypertensive rats and the mechanism and inhibitive method thereof. Methods: A neuroendocrine hypertensive model was established with adult Wistar rat. A total of 34 rats were randomly divided into four groups: parzosin (Hα), cilazapril (Hace), pentoxifylline(Hptx) and hypertensive control group(Hc). Ten normal-tensive Wistar rats were used as normal control (Nc). The systemic blood pressure, serum procollagen type Ⅲ level, serum TNF-α level, collagen volume fraction(CVF) were detected. Results: In Hace group, systolic pressure, left ventricular weight, the levels of serum procollagen type III and TNF-α were all reduced obviously compared to those in Hc group(P < 0.05). In Hα group, the systolic pressure and left ventricular weight were reduced obviously compared to those in Hc group(P < 0.05), however, the levels of serum procollagen type III and TNF-α were higher than those of Nc group(P < 0.05). In group Hptx, the systolic pressure and left ventricular weight were not decreased, while the levels of serum procollagen typeⅢ,TNF-α and CVF were reduced to normal levels. Conclusion:The angiotensin coverting enzyme inhibitor is the effective agent to reverse myocardial fibrosis, which can be achieved mostly by the inhibition of AngⅡ. Pentoxifylline may inhibit and reverse myocardial fibrosis which correlated with inhibiting TNF-α.