Zhou Xiao-Juan, Kong Xiang-Min, Wang Ying-Chao, Jiang Cheng, Jin Zhao-Xiang, Ai Le, Zhang Ling, Wang Yi
Department of Pharmacy, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.
Zhejiang Provincial Key Laboratory of Cardiovascular Disease Diagnosis and Treatment, Hangzhou 310009, China.
Zhongguo Zhong Yao Za Zhi. 2018 Dec;43(23):4672-4677. doi: 10.19540/j.cnki.cjcmm.20181031.002.
The aim of the present study is to evaluate the vasodilation effects of Tongmai Yangxin Pills (TMYX) on rat mesenteric artery as well as its mechanism of action. The relaxation effects of TMYX extracts with different concentrations were determined on isolated rat mesenteric artery in normal condition as well as pretreating by phenylephrine and KCl. Vascular relaxation effects of TMTX were also determined in mesenteric artery preincubated with L-ANME and indomethacin or in endothelium denuded mesenteric artery. Moreover, effects of TMYX by 50 mg·L⁻¹ on NO secretion and the phosphorylation of eNOS in a cellular model of human umbilical vein endothelial cell (HUVEC) pretreated with or without L-NAME were also observed. The experimental results showed that TMYX has no obvious effect on vasodilation of arteries in normal or KCl pretreated condition, while it can dose-dependently relax the rat mesenteric artery with intact endothelium stimulated with phenylephrine at a maximal diastolic rate of (64.71±10.03)%. After preincubating with L-NAME for 15 min or removal of mesenteric artery endothelium, the maximal diastolic rate was decreased to (35.77±8.93)% and (25.85±10.84)% respectively. However, preincubating with indomethacin had no inhibitory effect on TMYX induced vascular relaxation. Meanwhile, TMYX at 50 mg·L⁻¹ could increase the expression of P-eNOS and the secretion of NO in HUVEC. L-NAME significantly inhibited NO release and phosphorylation of eNOS induced by TMYX. The results suggested TMYX exerted endothelium-dependent relaxation effects against PE-induced contractions of isolated rat mesenteric artery through NO-cGMP signaling pathway.
本研究旨在评价通脉养心丸（TMYX）对大鼠肠系膜动脉的舒张作用及其作用机制。测定不同浓度TMYX提取物对正常状态以及用去氧肾上腺素和氯化钾预处理后的离体大鼠肠系膜动脉的舒张作用。还测定了在与L-硝基精氨酸甲酯（L-ANME）和吲哚美辛预孵育的肠系膜动脉或内皮剥脱的肠系膜动脉中TMYX的血管舒张作用。此外，还观察了50mg·L⁻¹TMYX对用或不用L-硝基精氨酸甲酯（L-NAME）预处理的人脐静脉内皮细胞（HUVEC）细胞模型中NO分泌和内皮型一氧化氮合酶（eNOS）磷酸化的影响。实验结果表明，TMYX在正常或氯化钾预处理条件下对动脉舒张无明显作用，而在去氧肾上腺素刺激下，它能剂量依赖性地舒张具有完整内皮的大鼠肠系膜动脉，最大舒张率为（64.71±10.03）%。用L-NAME预孵育15分钟或去除肠系膜动脉内皮后，最大舒张率分别降至（35.77±8.93）%和（25.85±10.84）%。然而，用吲哚美辛预孵育对TMYX诱导的血管舒张无抑制作用。同时，50mg·L⁻¹TMYX可增加HUVEC中磷酸化eNOS的表达和NO的分泌。L-NAME显著抑制TMYX诱导的NO释放和eNOS磷酸化。结果表明，TMYX通过NO-cGMP信号通路对去氧肾上腺素诱导的离体大鼠肠系膜动脉收缩发挥内皮依赖性舒张作用。
