葛根素对自发性高血压大鼠肠系膜动脉舒张功能的影响
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摘要
目的探究葛根素对自发性高血压大鼠肠系膜动脉舒张功能的影响。方法 20只自发性高血压大鼠随机分为5组:高血压组,卡托普利组,葛根素低、中、高剂量组,每组4只,另外4只WKY作为正常对照组。于给药前、给药8周后测量体重和血压,检测血清中NO和血浆中ET-1含量,分离肠系膜三级动脉做HE染色并计算管壁厚度/管腔半径(WT/LR)。利用离体血管压力直径测定仪检测葛根素对内皮完整和去内皮动脉环的舒张效应,并观察内皮依赖性途径阻滞剂和非内皮依赖性途径阻滞剂孵育后,葛根素对动脉环舒张作用的影响。结果与高血压组相比,葛根素低、中、高剂量组的收缩压差值和舒张压差值均降低。葛根素高剂量组血清NO含量下降、血浆ET-1含量升高。葛根素中、高剂量组肠系膜三级动脉WT/LR均下降。葛根素对内皮完整和去内皮的动脉环均有浓度依赖性舒张作用,但内皮完整动脉环舒张作用更强。内皮依赖性通路阻滞剂和非内皮依赖性通路阻滞剂孵育后,葛根素的舒张效应均下降。结论葛根素对自发性高血压大鼠肠系膜动脉的舒张效应同时具备内皮依赖性和非内皮依赖性。其内皮依赖性途径通过NO-sGC-cGMP信号通路途径来实现的,同时也与促进前列腺类物质释放有关。葛根素非内皮依赖性途径可能是与血管平滑肌上K~+通道开放有关。
Objective To investigate the effect of puerarin on the relaxation of mesenteric artery in spontaneously hypertensive rats. Methods 20 spontaneously hypertensive rats were randomly divided into5 groups: hypertension group, captopril group, puerarin low, medium and high dose groups, 4 in each group,and 4 WKY as a normal control group. Body weight and blood pressure were measured before administration and 8 weeks after administration,the content of NO in the serum and the content of ET-1 in the plasma were measured,separation of mesenteric tertiary arteries for HE staining, analysis of wall thickness-to-lumen radius ratios(WT/LR) were performed. The relaxation effect of puerarin on endothelium-intact and endothelium-denuded artery rings were measured by pressure myograph. The effect of puerarin on the relaxation of the arterial ring after endothelium-dependent pathway blockers and endothelium-independent pathway blockers after incubation. Results The systolic blood pressure difference and diastolic blood pressure difference in the low, medium and high dose groups of puerarin were significantly lower than the hypertension group. Serum NO content decreased and plasma ET-1 levels increased in the high dose group of puerarin. The WT/LR of the mesenteric tertiary arteries in the middle and high dose group of puerarin decreased. Puerarin had a concentration-dependent relaxation effect on endothelium-intact and endotheliumdenuded artery rings, but the endothelium-intact arterial ring diastolic effect was stronger. After incubation with endothelium-dependent pathway blockers and endothelium-independent pathway blockers, the relaxation effect of puerarin was significantly attenuated. Conclusion The vasodilating effect of puerarin on the mesenteric artery in spontaneously hypertensive rats is both endothelium-dependent and endotheliumindependent. The endothelium-dependent pathway is achieved through the NO-sGC-cGMP signaling pathway and is also associated with the promotion of prostatic release. The endothelium-independent pathway of puerarin may be related to the opening of K+ channels on vascular smooth muscle.
Objective To investigate the effect of puerarin on the relaxation of mesenteric artery in spontaneously hypertensive rats. Methods 20 spontaneously hypertensive rats were randomly divided into5 groups: hypertension group, captopril group, puerarin low, medium and high dose groups, 4 in each group,and 4 WKY as a normal control group. Body weight and blood pressure were measured before administration and 8 weeks after administration,the content of NO in the serum and the content of ET-1 in the plasma were measured,separation of mesenteric tertiary arteries for HE staining, analysis of wall thickness-to-lumen radius ratios(WT/LR) were performed. The relaxation effect of puerarin on endothelium-intact and endothelium-denuded artery rings were measured by pressure myograph. The effect of puerarin on the relaxation of the arterial ring after endothelium-dependent pathway blockers and endothelium-independent pathway blockers after incubation. Results The systolic blood pressure difference and diastolic blood pressure difference in the low, medium and high dose groups of puerarin were significantly lower than the hypertension group. Serum NO content decreased and plasma ET-1 levels increased in the high dose group of puerarin. The WT/LR of the mesenteric tertiary arteries in the middle and high dose group of puerarin decreased. Puerarin had a concentration-dependent relaxation effect on endothelium-intact and endotheliumdenuded artery rings, but the endothelium-intact arterial ring diastolic effect was stronger. After incubation with endothelium-dependent pathway blockers and endothelium-independent pathway blockers, the relaxation effect of puerarin was significantly attenuated. Conclusion The vasodilating effect of puerarin on the mesenteric artery in spontaneously hypertensive rats is both endothelium-dependent and endotheliumindependent. The endothelium-dependent pathway is achieved through the NO-sGC-cGMP signaling pathway and is also associated with the promotion of prostatic release. The endothelium-independent pathway of puerarin may be related to the opening of K+ channels on vascular smooth muscle.
引文
[1]秦小江.杜鹃素舒张大鼠主动脉及对自发性高血压大鼠主动脉损伤的保护作用[D].山西医科大学,2015.
[2]Mathiassen O,Buus N,Sihm I.Small artery structure is an independent predictor of cardiovascular events in essential hypertension[J].JHypertens,2007,25(25):1021-1026.
[3]Zhou Y,Zhang H,Peng C.Puerarin:A Review of Pharmacological Effects[J].Phytother Res,2014,28(7):961-975.
[4]Shahid M,Buys E.Assessing murine resistance artery function using pressure myography[J].J Vis Exp,2013(7):76.
[5]Xue W,Li Y,Li J,et al.Endothelium-dependent relaxation induced by etomidate in the aortas of insulin-resistant rats[J].Arch Med Sci,2018,14(5):1155-1162.
[6]闫奎坡.冠心Ⅱ号心脏保护作用的物质基础及其舒张大鼠胸主动脉机制的研究[D].中南大学,2012.
[7]许云飞,吴昀,李文春.益母草碱对大鼠肠系膜动脉的力学效应及其机制探讨[J].中国临床解剖学杂志,2017(5):548-553.
[8]隋海霞.芹菜素安全性和降血压作用及其机制的实验研究[D].中国疾病预防控制中心,2009.
[9]Mahobiya A,Singh T,Rungsung S.Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat isolated pulmonary artery[J].Pharmacol Rep,2018,70(5):863-874.
[10]姜雨鸽,汪海.血管平滑肌钾通道及其调节因素[J].中国药理学通报,2002(5):494-498.
[2]Mathiassen O,Buus N,Sihm I.Small artery structure is an independent predictor of cardiovascular events in essential hypertension[J].JHypertens,2007,25(25):1021-1026.
[3]Zhou Y,Zhang H,Peng C.Puerarin:A Review of Pharmacological Effects[J].Phytother Res,2014,28(7):961-975.
[4]Shahid M,Buys E.Assessing murine resistance artery function using pressure myography[J].J Vis Exp,2013(7):76.
[5]Xue W,Li Y,Li J,et al.Endothelium-dependent relaxation induced by etomidate in the aortas of insulin-resistant rats[J].Arch Med Sci,2018,14(5):1155-1162.
[6]闫奎坡.冠心Ⅱ号心脏保护作用的物质基础及其舒张大鼠胸主动脉机制的研究[D].中南大学,2012.
[7]许云飞,吴昀,李文春.益母草碱对大鼠肠系膜动脉的力学效应及其机制探讨[J].中国临床解剖学杂志,2017(5):548-553.
[8]隋海霞.芹菜素安全性和降血压作用及其机制的实验研究[D].中国疾病预防控制中心,2009.
[9]Mahobiya A,Singh T,Rungsung S.Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat isolated pulmonary artery[J].Pharmacol Rep,2018,70(5):863-874.
[10]姜雨鸽,汪海.血管平滑肌钾通道及其调节因素[J].中国药理学通报,2002(5):494-498.