缝隙连接蛋白40磷酸化介导自发性高血压大鼠脑基底动脉血管舒张功能
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摘要
目的研究自发性高血压大鼠(SHR)脑基底动脉缝隙连接蛋白40(Connexin 40, Cx40)磷酸化与血管舒张功能的变化关系。方法应用大鼠尾动脉无创血压测量技术测量Wistar大鼠和SHR尾动脉血压;压力机动图技术用于测量脑基底动脉直径的变化;免疫组织化学技术用于研究脑基底动脉平滑肌细胞Cx40的分布;Western blot技术用于研究SHR脑基底动脉平滑肌细胞Cx40的表达变化。结果相比Wistar大鼠,SHR收缩压升高(P<0.01,n=6);18β-GA抑制SNP介导的SHR脑基底动脉舒张作用减低(P<0.01,n=6);SHR脑基底动脉Cx40分布密度降低(P<0.01,n=6);SHR脑基底动脉Cx40表达下调,磷酸化Cx40表达上调(P<0.05,n=6)。结论 Cx40磷酸化,导致SHR脑基底动脉舒张功能降低,SHR收缩压上升。
Objective To investigated the correlation between phosphorylation of Cx40 and the vasodilative function in basilar artery of spontaneously hypertension rats(SHR). Methods Caudal artery sphygmomanometer technology was used to measure systolic pressure of Wistar rats and SHR. Pressure myograph system technology was used to research the change of diameter of basilar artery. Immunofluorescence technique was used to study distributed density of Cx40 in basilar artery. Western blot technique were used to study expression of Cx40 in basilar artery. Results Compared with Wistar rats, SHR systolic pressure was significantly increased(P<0.01, n=6). Compared with Wistar rats,The SNP mediated vasodilative function was significantly inhibited in basilar artery of SHR(P<0.01, n=6); immunofluorescence distributed density of Cx40 were significantly reduced(P<0.01, n=6); and expression of Cx40 was significantly down-regulated and phosphorylated Cx40 was significantly up-regulated(P<0.05, n=6). Conclusion Due to phosphorylation of Cx40 mediated vasodilative function is reduced in basilar artery, SHR systolic pressure increases.
Objective To investigated the correlation between phosphorylation of Cx40 and the vasodilative function in basilar artery of spontaneously hypertension rats(SHR). Methods Caudal artery sphygmomanometer technology was used to measure systolic pressure of Wistar rats and SHR. Pressure myograph system technology was used to research the change of diameter of basilar artery. Immunofluorescence technique was used to study distributed density of Cx40 in basilar artery. Western blot technique were used to study expression of Cx40 in basilar artery. Results Compared with Wistar rats, SHR systolic pressure was significantly increased(P<0.01, n=6). Compared with Wistar rats,The SNP mediated vasodilative function was significantly inhibited in basilar artery of SHR(P<0.01, n=6); immunofluorescence distributed density of Cx40 were significantly reduced(P<0.01, n=6); and expression of Cx40 was significantly down-regulated and phosphorylated Cx40 was significantly up-regulated(P<0.05, n=6). Conclusion Due to phosphorylation of Cx40 mediated vasodilative function is reduced in basilar artery, SHR systolic pressure increases.
引文
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[12] 张传林,丛丽娜,王蕊,等.大黄素增加BKCa通道β1亚基表达介导自发性高血压大鼠脑基底动脉舒张[J].生理学报,2014,66(3):289-294.
[13] Dukic A,Haugen LH,Pidoux G,et al.A protein kinase A-ezrin complex regulates connexin 43 gap junction communication in liver epithelial cells[J].Cell Signal,2017,32:1-11.
[14] Wu D,Li B,Liu H,et al.In vitro inhibited effect of gap junction composed of Cx43 in the invasion and metastasis of testicular cancer resistanced to cisplatin[J].Biomed Pharmacother,2018,98:826-833.
[15] Wei J,Li Y,Jiao Q,et al.Influence of sodium nitroprusside on expressions of FBXL5 and IRP2 in SH-SY5Y cells[J].Acta Physiologica Sinica,2017,69(3):261-266.
[2] Garciarena CD,Malik A,Swietach P,et al.Distinct moieties underlie biphasic H+ gating of connexin43 channels,producing a pH optimum for intercellular communication[J].FASEB J,2018,32(4):1969-1981.
[3] Kolosov D,Piermarini PM,O′ Donnell MJ.Malpighian tubules of Trichoplusia ni:recycling ions via gap junctions and switching between secretion and reabsorption of Na+ and K+ in the distal ileac plexus[J].J Exp Biol,2018,221(Pt 5).pii:jeb172296.
[4] Mohanty I,Parija SC,Suklabaidya S,et al.Acidosis potentiates endothelium dependent vasorelaxation and gap junction communication in the superior mesenteric artery[J].Eur J Pharmacol,2018,15(827):22-31.
[5] Ye WG,Yue B,Aoyama H,et al.Junctional delay,frequency,and direction-dependent uncoupling of human heterotypic Cx45/Cx43 gap junction channels[J].J Mol Cell Cardiol,2017,111:17-26.
[6] Denis JF,Scheckenbach K,Pfenniger A,et al.Connexin40 controls endothelial activation by dampening NFκB activation[J].Oncotarget,2017,8(31):50972-50986.
[7] Lanpe PD,Lau AF.Regulation of gap junctions by phosphorylation of connexins[J].Arch Biochem Biophys,2000,384(2):205-215.
[8] Le Gal L,Alonso F,Wagner C,et al.Restoration of connexin 40 (Cx40) in Renin-producing cells reduces the hypertension of Cx40 null mice[J].Hypertension,2014,63(6):1198-1204.
[9] 章艳萍,王元媛,干艳捷,等.茜草素介导BK(Ca)通道beta亚基功能舒张肾叶间动脉降低SHR收缩压[J].实用医学杂志,2017,33(22):3706-3709.
[10] 王蕊,马克涛,司军强,等.18-β甘草次酸抑制KCl对大鼠脑中动脉的收缩作用[J].石河子大学学报:自然科学版,2013,31(6):707-710.
[11] 罗勇,陈小伍,朱达坚,等.细胞自噬在姜黄素增强LoVo细胞对伊立替康化疗敏感性中的作用[J].实用医学杂志,2017,33(6):871-875.
[12] 张传林,丛丽娜,王蕊,等.大黄素增加BKCa通道β1亚基表达介导自发性高血压大鼠脑基底动脉舒张[J].生理学报,2014,66(3):289-294.
[13] Dukic A,Haugen LH,Pidoux G,et al.A protein kinase A-ezrin complex regulates connexin 43 gap junction communication in liver epithelial cells[J].Cell Signal,2017,32:1-11.
[14] Wu D,Li B,Liu H,et al.In vitro inhibited effect of gap junction composed of Cx43 in the invasion and metastasis of testicular cancer resistanced to cisplatin[J].Biomed Pharmacother,2018,98:826-833.
[15] Wei J,Li Y,Jiao Q,et al.Influence of sodium nitroprusside on expressions of FBXL5 and IRP2 in SH-SY5Y cells[J].Acta Physiologica Sinica,2017,69(3):261-266.