外源性硫化氢对L—NAME诱导的高血压大鼠主动脉舒张功能的影响

Effect of exogenous hydrogen sulfide on the relaxation of aorta in L -NAME -induced hypertension in rats

目的观察硫化氢（H2S）预处理对高血压大鼠主动脉功能的影响。方法健康雄性SD大鼠，随机分为4组（每组n=10）。①对照组，自由饮自来水；②硫氢化钠（NaHS）组，腹腔注射NaHS溶液（10μmol·kg^-·d^-1）；③L-硝基-精氨酸甲酯（L-NAME）组，L-NAME溶于自来水自由饮水喂养；④NaHS＋L—NAME组，腹腔注射NaHS溶液（10μmol·kg^-1·d^-1），L—NAME溶于自来水自由喂养。每组处理时间为14天。PowerLab系统测定大鼠离体主动脉血管舒张功能；Western blot测定大鼠主动脉胱硫醚-γ-裂解酶（CSE）的表达；生化方法测定大鼠血清H2S浓度；苏木精-伊红染色、Elastic Van Gieson（EVG）染色观察大鼠主动脉管壁厚度、管壁结构、弹性纤维及胶原纤维的变化。结果与对照组比较，L-NAME组大鼠血管舒张功能明显减弱（P〈0．05），血清H2S浓度降低（P〈0．05），主动脉CSE的表达减少（P〈0．05）。NaHS预处理14天可以逆转L—NAME的作用，上调主动脉CSE的表达，增加血清中H2S的浓度，改善乙酰胆碱（ACh）引起的内皮依赖性血管舒张作用（P〈0．05）。但是各组大鼠主动脉管壁厚度、管壁结构、胶原纤维和弹性纤维等未见明显变化。结论外源性NaHS预处理可以上调大鼠主动脉中CSE的表达，增加血清H2S的浓度，提高主动脉的舒张功能。

Objective To investigate the effect of exogenous hydrogen sulfide （ H2S） on the function of aorta from N -nitro- L- arginine methyl ester （L- NAME） -induced hypertension rats. Methods Healthy male SD rats were di- vided into four groups （n = 10 each）： control group （feed with tap water freely）, sodium hydrogen sulfide （NariS） group （NariS solution was injected peritonially at 10μmol·kg^-1·d^-1）, L- NAME group （feed with L- NAME dissolved in tap water freely） , and L - NAME ＋ NariS group （feed with L - NAME dissolved in tap water freely, NariS so- lution was injected peritonially at 10 μmol·kg^-1·d^-1）. All groups were treated with tap water, NariS, L - NAME, or NariS ＋ L - NAME respectively for 14 days. The tension of isolated thoracic aorta rings perfused with different concentrations of aeetylcholine （ACh） was measured by PowerLab system. The expression of cystathionine -γ-lyase （CSE） in aorta was detected by Western blot. The level of serum H2S was detected using biochemical method. Morphological changes of vessel wall thickness, constitution, elastic and collagen fibers in aorta were examined by hematoxylin -eosin and Elastic Van Gieson （EVG） stain. Results Compared with control group, vasodilation in L- NAME group attenuated obviously （ P 〈 0.05 ） ; The concentration of H2 S in serum and the expression of CSE in thoracic aorta also reduced （ P 〈 0.05）. Pre- treatment with NariS can inverse the effect of L - NAME, which was mediated by upregrulating the expression of CSE in thoracic aorta, further increased the concentration of H2S in serum and improved the dilation of the thoracic aorta （P 〈 0.05 ）. However, no significant changes were observed in vessel wall thickness, constitution, elastic fibers and collagen fi- bers in aorta among all groups. Conclusion Exogenous H2 S exerts vasodilation effect on the aorta of L - NAME - induced hypertension in rats as a result of up- regulating the expression of CSE and increasing the concentration of HzS in serum.