自发性高血压大鼠硫化氢/胱硫醚γ-裂解酶体系的实验观察

Changes and significance of hydrogen sulfide/cystathionine γ-lyase system in hypertension: an experimental study with rats

目的 探讨硫化氢 /胱硫醚γ 裂解酶 (H2 S/CSE)体系在自发性高血压形成及发展中的变化及重要作用。方法 4周龄雄性正常血压大鼠 (WKY) 8只 ,作为WKY对照组 (n =8) ,自发性高血压大鼠 (SHR) 16只 ,随机分为SHR对照组 (n =8)及SHR +NaHS(外源性H2 S供体 )组 (n =8) ,其中SHR +NaHS组每日腹腔注射NaHS ,WKY对照组及SHR对照组注射同样剂量的生理盐水。相同条件下饲养 5周后 ,检测其血压、左心与全心重量比 ,血浆H2 S水平、胸主动脉CSEmRNA转录水平以及胸主动脉显微结构。结果 9周龄时SHR对照组大鼠血压显著高于WKY对照组大鼠 [(184±12 )mmHgvs (10 8± 2 3)mmHg ,1mmHg =0 .133kPa],左心与全心比值大于WKY对照组[(0 85 3± 0 0 2 1)vs (0 82 6± 0 0 2 4 ) ],胸主动脉CSEmRNA转录水平及血浆H2 S水平均低于WKY对照组大鼠 [(9 3± 0 7)× 10 -8fmolvs (16 1± 1 0 )× 10 -8fmol]及 [(2 0± 9) μmol/Lvs (4 8± 13)μmol/L],而胸主动脉显微结构结果显示胸主动脉外径、中膜面积、壁厚腔径比均大于WKY对照组大鼠 [外径 (1999± 4 5 ) μmvs (1790± 96 ) μm],中膜面积 (0 6 0± 0 0 6 )mm2 vs (0 4 8± 0 0 3)mm2 ,壁厚腔径比 (0 0 6 6± 0 0 0 6 )vs (0 0 6 0± 0 0 0 4 )。

Objective To explore the significance of hydrogen sulfide/ cystathionine γ-lyase (H 2S/CSE) system in the development of hypertension and the effects of H 2S/CSE system on the modulation of aortic remodeling process of hypertension. Methods Eight 4-week-old male WKY rats were used as WKY control group, and another sixteen SHR rats at the age of 4 weeks were randomly divided into SHR control group (n=8) and SHR+NaHS(H 2S donor) group (n=8). The rats of SHR control and WKY control were injected with normal saline and the rats of the SHR+NaHS group were injected with NaHS each day. Five weeks later, the blood pressure and the left-to-whole heart weight ratio were determined. The transcriptional level of CSE in aorta and the H 2S level in plasma were detected. The morphometric parameters of the thoracic aorta including the outer radius, medium area and ratio of wall thickness to lumen radius were detected too. Results At the age of 9 weeks the systolic blood pressure and the left-to-whole heart weight ratio of the SHR control rats were both higher than those of the WKY control rats [(184±12) mm Hg vs (108±23) mm Hg,1 mm Hg=0.133 kPa, and (0.853±0.021) vs (0.826±0.024)]. The transcriptional level of CSE in aorta and the H 2S level in serum of the rats in the SHR control group were both lower than those of the rats in the WKY control group(9.3±0.7)×10 -8 fmol vs (16.1±1.0)×10 -8 fmol, and (20±9) μmol/L vs (48±13) μmol/L, while the morphometric parameters of the thoracic aorta including the outer radius, the medium area and ratio of lumen radius and wall thickness of the SHR control rats were all higher compared with those of the WKY control rats [outer radius: (1999±45) μm vs (1790±96) μm],medium area: (0.60±0.06) mm2 vs (0.48±0.03) mm2, and ratio of wall thickness to lumen radius: (0.066±0.006) vs (0.060±0.004). The exogenous administration of NaHS made the systolic blood pressure of rats in the SHR+ NaHS group much lower than that of the rats in SHR control group [(158±13) mm Hg vs (184±12) mm Hg], however, the transcriptional level of CSE in aorta and the H 2S level in serum of the rats in SHR+ NaHS group were much higher than those of the rats in SHR control group [(12.4±1.0)×10 -8 fmol vs (9.3±0.7)×10 -8 fmol] vs [(96±32) μmol/L vs (20± 9) μmol/L]. The morphometrc parameters of SHR+ NaHS group were lower than those of the SHR control group. Conclusion Down regulation of H 2S/CSE system is a major factor in the development of spontaneous hypertension and the accompanying structural remodeling of aorta. Exogenous administration of H 2S may attenuate the process of hypertension.