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目的观察充血性心力衰竭(CHF)大鼠交感神经系统(SNS)的变化,探讨厄贝沙坦(Irbesartan)对MI后CHF大鼠SNS的影响及相应的心肌保护机制。方法选用雄性Sprague-Dawley大鼠,体重在250g左右。结扎大鼠冠状动脉前降支(假手术组只穿线不结扎)制备心肌梗死(MI)后心力衰竭模型。实验大鼠分3组:假手术组(n=8);心衰对照组(n=8);厄贝沙坦治疗组(n=8)。术后24h内开始给药,治疗组给予厄贝沙坦50mg/(kg·d)灌胃,疗程6周。术后6周记录左心室短轴缩短率(FS)、射血分数(EF);测定血浆B型利钠肽(BNP)、肾上腺素(E)、去甲肾上腺素(NE);测定心肌组织BNP、β1受体密度。结果心衰组大鼠的FS、EF值均明显低于厄贝沙坦组、假手术组分别为[(13.34±3.61)%、(40.2±6.72)%和(47.6±9.87)%;(26.9±7.73)%、(49.7±8.79)%和(76.7±11.5)%,P<0.01]。心衰组大鼠血浆及心肌组织BNP含量均明显高于假手术组[血浆BNP分别为(47.76±9.50)pg/mL、(13.5±21.9)pg/mL;心肌BNP分别为(40.5±10.2)pg/mgPro.、(8.04±1.90)pg/mgPro.,P<0.01],厄贝沙坦组大鼠血浆及心肌组织BNP含量明显低于心衰组[分别为血浆(27.05±6.09)pg/mL、心肌(31.1±6.37)pg/mgPro.,P<0.01]。心衰组大鼠血浆E、NE水平均明显高于假手术组[E水平分别为(5.15±0.96)μg/L、(2.18±0.63)μg/L;NE水平分别为(18.77±5.02)μg/L、(5.44±1.55)μg/L,P<0.01],而厄贝沙坦组明显低于心衰组[E为(12.16±2.13)μg/L、为NE为(3.44±0.93)μg/L,P<0.01],且循环E与心肌BNP呈正相关。心衰组大鼠Binding值、Bmax均低于假手术组[(8.43±5.09)fmol/mgPro.、(14.21±8.32)fmol/mgPro.;(16.37±2.02)fmol/mgPro.、(26.51±2.18)fmol/mgPro.],特别是Bmax差异有显著性,厄贝沙坦组Binding、Bmax[(11.91±7.25)fmol/mgPro.、(22.70±3.12)fmol/mgPro.]明显高于心衰组(P<0.01)。心衰组Kd明显高于假手术组[(6.47±0.62)nM、(5.76±0.82)nM],而厄贝沙坦组[(6.45±0.88)nM]明显低于心衰组(P<0.01)。结论心衰大鼠SNS激活,出现β-受体减敏现象,且心力衰竭程度与β-受体减敏呈正相关。厄贝沙坦抑制SNS过度激活、减轻β-受体减敏是其保护心肌、治疗心力衰竭的重要机制之一。
Objective To observe the changes of the sympathetic nervous system (SNS) in rats with congestive heart failure (CHF) and to explore the effects of Irbesartan on the SNS of CHF rats after MI and the related mechanisms of myocardial protection. Methods Male Sprague-Dawley rats weighing about 250g were used. The anterior descending coronary artery was ligated in the sham-operation group, and the heart failure model was established after myocardial infarction (MI). The experimental rats were divided into 3 groups: sham operation group (n = 8), heart failure control group (n = 8) and irbesartan treatment group (n = 8). Administration began within 24 hours after operation, and the treatment group received irbesartan 50 mg / (kg · d) orally for 6 weeks. Left ventricular fractional shortening (FS) and ejection fraction (EF) were recorded 6 weeks after operation. Plasma BNP, NE and NE were measured. BNP, β1 receptor density. Results The FS and EF values of heart failure group were significantly lower than those of irbesartan group ([(13.34 ± 3.61)%, (40.2 ± 6.72)% and (47.6 ± 9.87)%, respectively] ± 7.73)%, (49.7 ± 8.79)% and (76.7 ± 11.5)% respectively, P <0.01]. BNP levels in plasma and myocardial tissue in CHF group were significantly higher than those in sham group [(47.76 ± 9.50) pg / mL and (13.5 ± 21.9) pg / mL, respectively; BNP in myocardium were (40.5 ± 10.2) (P <0.05). The levels of BNP in plasma and myocardial tissue in irbesartan group were significantly lower than those in heart failure group [(27.05 ± 6.09) pg / mgPro, mL, myocardium (31.1 ± 6.37) pg / mgPro., P <0.01]. The levels of plasma E and NE in heart failure group were significantly higher than those in sham operation group [(5.15 ± 0.96) μg / L and (2.18 ± 0.63) μg / L, respectively, and the NE levels were (18.77 ± 5.02) μg /L,(5.44 ± 1.55μg / L, P <0.01], while irbesartan group was significantly lower than that of heart failure group [E (12.16 ± 2.13) μg / L, NE was (3.44 ± 0.93) μg /L,P<0.01], and the cycle E and myocardial BNP was positively correlated. The Binding value and Bmax in heart failure group were significantly lower than those in sham operation group [(8.43 ± 5.09) fmol / mgPro., (14.21 ± 8.32) fmol / mgPro., (16.37 ± 2.02) fmol / mgPro ) fmol / mgPro.], especially the Bmax difference was significant, irbesartan group Binding, Bmax [(11.91 ± 7.25) fmol / mgPro., (22.70 ± 3.12) fmol / mgPro. (P <0.01). Kd in heart failure group was significantly higher than that in sham operation group [(6.47 ± 0.62) nM, (5.76 ± 0.82) nM], while that in irbesartan group was significantly lower than that in heart failure group (P <0.01) ). Conclusions SNS is activated in heart failure rats, and β-receptor desensitization appears, and the degree of heart failure is positively correlated with β-receptor desensitization. Irbesartan inhibit SNS over-activation, reduce β-receptor desensitization is one of the important mechanisms of myocardial protection, treatment of heart failure.