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[硫化氢改善慢性心力衰竭大鼠的心功能和心脏结构]

[Sodium hydrosulfide improves cardiac functions and structures in rats with chronic heart failure].

作者信息

Li Xiao-hui, Zhang Chao-ying, Zhang Ting

机构信息

Department of Cardiovascular Diseases, Children's Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2011 Nov 22;91(43):3044-9.

PMID:22333056
Abstract

OBJECTIVE

To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling.

METHODS

A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared.

RESULTS

At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P < 0.05, 1 mm Hg = 0.133 kPa). The RV peak rate of contraction and relaxation markedly decreased (RV ± dp/dt max) (mm Hg/s: 1528 ± 113 vs 2336 ± 185 and 1835 ± 132, 1331 ± 107 vs 2213 ± 212 and 1768 ± 116, all P < 0.05). It was found microscopically that myocardial fibers in the shunt group were irregularly arranged, partially cytolysis and infiltrated by inflammatory cells. Electron microscopy revealed that myocardial fibers thickened non-uniformly in the shunt group, some fiber mitochondria were highly swollen and contained vacuoles. And sarcoplasmic reticulum appeared slightly dilated. Polarized microscopy indicated that, collagen content (particularly type-I collagen) increased in the shunt group compared with the sham operation group. Additionally, compared with the shunt group, the shunt and NaHS treatment groups showed an amelioration of myocardial damage, an alleviation of myocardial fiber changes and a decrease in myocardial collagen content (particularly type-I collagen). Compared with the sham operation and shunt + NaHS groups, the shunt group displayed increased right ventricular hydroxyproline (mg×g(-1)·pro: 1.32 ± 0.25 vs 0.89 ± 0.18 and 0.83 ± 0.19, all P < 0.05).

CONCLUSION

H(2)S may improve cardiac functions and ameliorate cardiac structures in rats with chronic heart failure probably through dilating the blood vessels and affecting the extracellular collagen metabolism.

摘要

目的

探讨硫化氢(H₂S)供体硫氢化钠(NaHS)对容量负荷诱导的慢性心力衰竭大鼠心功能和结构的影响,并研究其对心脏重塑的作用。

方法

将47只体重120 - 140 g的SD大鼠随机分为5组:分流组(n = 11)、假手术组(n = 8)、分流 + NaHS组(n = 10)、假手术 + NaHS组(n = 8)和分流 + 酚妥拉明组(n = 10)。采用腹主动脉 - 下腔静脉穿刺法建立慢性心力衰竭大鼠模型。术后8周,分析血流动力学参数、心肌组织的微观结构和超微结构。天狼星红染色后分析心肌组织细胞外胶原含量。测定并比较右心室羟脯氨酸浓度。

结果

术后8周,与假手术组和分流 + NaHS组相比,分流组右心室收缩压(RVSP)和右心室舒张末期压力(RVEDP)显著升高(mmHg:35.2 ± 3.9 vs 21.4 ± 3.7和28.1 ± 2.7,32 ± 5 vs 21 ± 4和26 ± 4,均P < 0.05,1 mmHg = 0.133 kPa)。右心室峰值收缩和舒张速率(RV ± dp/dt max)明显降低(mmHg/s:1528 ± 113 vs 2336 ± 185和1835 ± 132,1331 ± 107 vs 2213 ± 212和1768 ± 116,均P < 0.05)。显微镜下发现,分流组心肌纤维排列不规则,部分细胞溶解并有炎性细胞浸润。电镜显示,分流组心肌纤维不均匀增粗,部分纤维线粒体高度肿胀并含有空泡。肌浆网轻度扩张。偏振光显微镜显示,与假手术组相比,分流组胶原含量(尤其是I型胶原)增加。此外,与分流组相比,分流 + NaHS治疗组心肌损伤有所改善,心肌纤维变化减轻,心肌胶原含量(尤其是I型胶原)降低。与假手术组和分流 + NaHS组相比,分流组右心室羟脯氨酸升高(mg×g⁻¹·pro:1.32 ± 0.25 vs 0.89 ± 0.18和0.83 ± 0.19,均P < 0.05)。

结论

H₂S可能通过扩张血管和影响细胞外胶原代谢来改善慢性心力衰竭大鼠的心功能并减轻心脏结构改变。

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引用本文的文献

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Hydrogen sulfide upregulates heme oxygenase-1 expression in rats with volume overload-induced heart failure.硫化氢上调容量负荷诱导的心力衰竭大鼠血红素加氧酶-1的表达。
Biomed Rep. 2013 May;1(3):454-458. doi: 10.3892/br.2013.87. Epub 2013 Mar 26.
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Hydrogen sulfide suppresses the expression of MMP-8, MMP-13, and TIMP-1 in left ventricles of rats with cardiac volume overload.
硫化氢抑制心脏负荷过重大鼠左心室中 MMP-8、MMP-13 和 TIMP-1 的表达。
Acta Pharmacol Sin. 2013 Oct;34(10):1301-9. doi: 10.1038/aps.2013.84. Epub 2013 Aug 26.