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为探讨心力衰竭诱导的血管舒缩功能紊乱的相关机制,本实验对心梗后大鼠慢性心力衰竭(chronic heart failure,CHF)模型胸主动脉血管环的舒缩功能变化及可能的病理学机制进行了研究。将Sprague-Dawley大鼠随机分为两组:假手术(sham)组和慢性心衰(CHF)组。通过冠脉结扎法制作大鼠CHF模型。手术10周后,检测大鼠血流动力学指标及相关参数,之后迅速取出心脏并称重,TTC染色法检测心梗面积。制备大鼠胸主动脉环,利用敏感的肌张力描记技术,比较sham组和CHF组胸主动脉环的舒缩功能,观察血管环对KCl、CaCl2、苯肾上腺素(phenyle phrine,PE)和咖啡因(caffeine)的收缩反应以及对乙酰胆碱(acetylcholine,ACh)的舒张反应。并进一步研究一氧化氮合酶(nitricoxide synthase,NOS)抑制剂N-硝基-L-精氨酸甲酯(N-nitrl-L-arginine methylester,L-NAME)和非选择性环氧合酶(cyclooxy genase,COX)抑制剂吲哚美辛(indomethacin,Indo)对两组胸主动脉环ACh的反应曲线的影响。结果显示:(1)与sham组相比,CHF组大鼠胸主动脉环对血管收缩剂KCl(5～100mmol/L)和PE(1×10-8～3×10-4mol/L)的反应性明显提高,对血管舒张剂ACh(1×10-12～1×10-4mol/L)的反应性显著性降低(P<0.01,P<0.05);(2)L-NAME(1mmol/L)预处理后,CHF组血管对ACh(1×10-7～1×10-4mol/L)介导的内皮依赖性收缩明显增强(P<0.05),加入Indo(10μmol/L)后该现象消失;(3)与Indo未处理组相比,Indo(10μmol/L)预处理后,CHF组血管对ACh(1×10-12～1×10-4mol/L)介导的舒张反应明显增强(P<0.05);(4)在无钙K-H液中,与sham组相比,CHF组血管对CaCl2(1×10-4～3×10-2mol/L)介导的钙依赖性收缩曲线明显左移(P<0.05);caffeine(30mmol/L)诱导的血管收缩未见显著性变化。以上结果表明,CHF大鼠的胸主动脉血管环收缩异常与内皮功能障碍有关,其机制可能是通过血管内皮细胞COX途径提高内皮收缩因子,和(或)通过电压依赖性钙通道增加外钙流入引起血管收缩性能提高。
In order to explore the mechanism of heart failure-induced vasomotor dysfunction, the present study investigated the changes in the vasorelaxation and systolic and diastolic function of the thoracic aortic rings in the rat model of chronic heart failure (CHF) after myocardial infarction and the possible pathological mechanisms Were studied. Sprague-Dawley rats were randomly divided into two groups: the sham group and the chronic heart failure (CHF) group. The rat CHF model was made by coronary ligation. After 10 weeks of operation, the indexes of hemodynamics and related parameters of the rats were detected, and then the heart was quickly removed and weighed. The area of myocardial infarction was detected by TTC staining. The thoracic aortic rings of rats were prepared and the contractile and diastolic function of the thoracic aortic rings were compared between the sham group and the CHF group by using the sensitive muscle tension mapping technique. The effects of vascular rings on KCl, CaCl2, phenylephrine (PE) and coffee The contractile response to caffeine and the relaxation response to acetylcholine (ACh). The effects of N-nitrl-L-arginine methylester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and nonselective cyclooxygenase (cyclooxygenase (COX) inhibitor indomethacin (indomethacin, Indo on the thoracic aortic ring ACh response curve. The results showed that: (1) Compared with the sham group, the thoracic aortic rings of CHF group had significant effects on the contraction of vasoconstrictors KCl (5-100 mmol / L) and PE (1x10-8-3x10-4 mol / L) (P <0.01, P <0.05); (2) L-NAME (1mmol / L) significantly increased the reactivity to ACh (1 × 10-12 ~ L), the endothelium-dependent contraction mediated by ACh (1 × 10-7 ~ 1 × 10-4 mol / L) was significantly increased in CHF group (P <0.05). After adding Indo (10μmol / L) (3) Compared with Indo untreated group, pretreatment with Indo (10μmol / L), the vasorelaxation response of CHF group to ACh (1 × 10-12 ~ 1 × 10-4mol / L) was obvious (4) In the calcium-free KH solution, compared with the sham group, the calcium-dependent contraction induced by CaCl2 (1 × 10-4 ~ 3 × 10-2mol / L) The curve was significantly shifted to the left (P <0.05); no significant changes were observed in the vasoconstriction induced by caffeine (30 mmol / L). The above results suggest that the abnormal thoracic aortic ring contraction in CHF rats is associated with endothelial dysfunction. The mechanism may be that endothelial-cell factor (COX) may increase endothelial contraction factor and / or increase calcium influx via voltage-dependent calcium channels Cause vasoconstriction performance increase.