Wu Sheng-ying, Pan Chun-shui, Geng Bin, Zhao Jing, Yu Fang, Pang Yong-zheng, Tang Chao-shu, Qi Yong-fen
Institute of Cardiovascular Disease, Peking University First Hospital. Beijing 100034 China.
Acta Pharmacol Sin. 2006 Mar;27(3):299-306. doi: 10.1111/j.1745-7254.2006.00283.x.
To investigate the role of the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H2S) pathway in vascular calcification in vivo.
A rat vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN). The amount of CSE and osteopontin (OPN) mRNA was determined by using semi-quantitative reverse-transcription polymerase chain reaction. The calcium content, 45Ca2+ accumulation and alkaline phosphatase (ALP) activity were measured. H2S production and CSE activity were measured.
von Kossa staining produced strong positive black/brown staining in areas among the elastic fibers of the medial layer in the calcified aorta. The calcium content, 45Ca2+ accumulation and ALP activity in calcified arteries increased by 6.77-, 1.42-, and 1.87-fold, respectively, compared with controls. The expression of the OPN gene was upregulated (P<0.01). Expression of the CSE gene was downregulated. However, calcium content, 45Ca2+ uptake and ALP activity in the VDN plus NaHS group was lower than that in the VDN group. The content of calcium and 45Ca2+ accumulation and activity of ALP in the aorta were 34.8%, 40.75% and 63.5% lower in the low-dosage NaHS group than in the VDN group, respectively (P<0.01), and the calcium content and deposition of 45Ca2+ and activity of ALP was 83.9%, 37.8 % and 46.2% lower in the aorta in the high-dosage NaHS group than in the VDN group, respectively (P<0.01). The expression of the OPN gene was downregulated.
The production of H2S, and CSE activity were decreased and CSE gene expression was downregulated in rats with vascular calcification. H2S can ameliorate vascular calcification, suggesting that the H2S/CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.
研究内源性胱硫醚γ-合酶（CSE）/硫化氢（H₂S）通路在体内血管钙化中的作用。
通过给予维生素D₃加尼古丁（VDN）建立大鼠血管钙化模型。采用半定量逆转录聚合酶链反应测定CSE和骨桥蛋白（OPN）mRNA的量。测量钙含量、⁴⁵Ca²⁺蓄积量和碱性磷酸酶（ALP）活性。测量H₂S生成量和CSE活性。
von Kossa染色在钙化主动脉中层弹性纤维之间的区域产生强阳性黑/棕色染色。与对照组相比，钙化动脉中的钙含量、⁴⁵Ca²⁺蓄积量和ALP活性分别增加了6.77倍、1.42倍和1.87倍。OPN基因的表达上调（P<0.01）。CSE基因的表达下调。然而，VDN加NaHS组的钙含量、⁴⁵Ca²⁺摄取量和ALP活性低于VDN组。低剂量NaHS组主动脉中的钙含量、⁴⁵Ca²⁺蓄积量和ALP活性分别比VDN组低34.8%、40.75%和63.5%（P<0.01），高剂量NaHS组主动脉中的钙含量、⁴⁵Ca²⁺沉积量和ALP活性分别比VDN组低83.9%、37.8%和46.2%（P<0.01）。OPN基因的表达下调。
血管钙化大鼠体内H₂S生成量和CSE活性降低，CSE基因表达下调。H₂S可改善血管钙化，提示H₂S/CSE通路在血管钙化发病机制中起调节作用。
