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河北医学  2022, Vol. 28 Issue (8): 1251-1255    DOI: 10.3969/j.issn.1006-6233.2022.08.04
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雷米普利通过激活ERK1/2-Cx43信号通路降低SHR大鼠的血压
赵亮, 魏童
新疆医科大学第五附属医院, 新疆 乌鲁木齐 830011
Ramipril Reduces Blood Pressure in SHR Rats by Activating ERK1/2-Cx43 Signaling Pathway
ZHAO Liang, WEI Tong
The Fifth Affiliated Hospital of Xinjiang Medical University, Xinjiang Urumqi 830011, China
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摘要 目的: 研究血管紧张素转换酶抑制剂雷米普利(Ramipril,RMP)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)血压的影响并探讨机制。方法: 50只雄性SHR大鼠随机分为SHR组、RMP+SHR组、RMP+甘珀酸[CBX,缝隙连接蛋白43(Cx43)抑制剂]+SHR组、RMP+U0126[细胞外信号调节激酶1/2(ERK1/2)抑制剂)]+SHR,RMP+CBX+U0126+SHR组,n=10/组。健康wistar大鼠为control组(n=10)并与SHR组均给予生理盐水40mL/kg i.v.,其余3组分别给予RMP 10mg/kg i.v.,RMP 10 mg/kg和CBX 13.5mg/kg i.v.,RMP 10mg/kg和CBX 13.5mg/kg和U012612mg/kg i.v.,尾静脉推注,给药48 h后采用BP-6大鼠无创血压测试仪、苏木精伊红染色和Western blot分析方法,观察大鼠生理指标的变化。结果: 与Control组比,SHR组大鼠呈高血压症状(均P<0.05),且Cx43的Ser368磷酸化水平(p-Cx43)和磷酸化的ERK1/2(p-ERK1/2)的表达水平下调(均P<0.05)。与SHR组比,RMP+SHR组的血压降低(均P<0.05),p-Cx43和p-ERK1/2的表达增加(均P<0.05)。与RMP+SHR组比,RMP+CBX+SHR组的血压增高, p-Cx43表达降低(均P<0.05),p-ERK1/2的表达无明显变化(P>0.05);与RMP+SHR组比, RMP+U0126+SHR组的血压明显增高,且p-Cx43和p-ERK1/2的表达都降低(均P<0.05)。与RMP+CBX+SHR组或RMP+U0126+SHR组比,RMP+CBX+U0126+SHR组的血压增高,而且p-Cx43和p-ERK1/2的表达都降低(均P<0.05)。结论: 本研究证实RMP可以通过激活ERK1/2-Cx43信号通路改善SHR大鼠的高血压症状。
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赵亮
魏童
关键词 雷米普利细胞外信号调节激酶1/2缝隙连接蛋白43自发性高血压大鼠    
AbstractObjective: To observe the effects of angiotensin converting enzyme inhibitor Ramipril (RMP) on blood pressure in spontaneously hypertensive rats (SHR) and explore the mechanism.Methods: Fifty male SHR rats were randomly divided into SHR group, RMP+SHR group, RMP+ gamperic acid [CBX, GAP junction 43 (Cx43) blocker] +SHR group, RMP+CBX+U0126[extra cellular signal-regulated kinase 1/2 (ERK1/2) inhibitor]+SHR, n=10/ group. control group (n=10) and SHR group were given normal saline 40mL/kg i.v. The other three groups were given RMP 10mg/kg i.v., RMP 10mg/kg+CBX 13.5mg/kg i.v., RMP 10mg/kg +CBX 13.5mg/kg+U012612mg/kg i.v., respectively. After 48 h of administration, BP-6 rat noninvasive blood pressure tester, hematoxylin eosin staining and Western blot analysis were used to observe the changes of physiological indexes of rats.Results: Compared with control group, SHR group showed hypertension symptoms (all P<0.05), and the phosphorylation level of Ser368 Cx43 (p-Cx43) and phosphorylation of ERK1/2 (p-ERk1/2) were down-regulated (all P<0.05). Compared with SHR group, the blood pressure of RMP+SHR group was decreased (all P<0.05), and the expressions of p-Cx43 and p-ERK1/2 were increased (all P<0.05). Compared with RMP+SHR group, the blood pressure of RMP+CBX+SHR group was significantly increased, and the expression of P-Cx43 was decreased (all P<0.05), while the expression of p-ERK1/2 was not significantly changed (P>0.05), while the blood pressure of RMP+U0126+SHR group was significantly increased. The expression of p-Cx43 and p-ERK1/2 was decreased (P<0.05). Compared with RMP+CBX+SHR group or RMP+U0126+SHR group, the blood pressure in RMP+CBX+U0126+SHR group was increased, and the expression of p-Cx43 and p-ERK1/2 was decreased (all P<0.05). Conclusion: This study confirmed that RMP can improve the symptoms of hypertension in SHR by activating ERK1/2 -Cx43 signaling pathway.
Key wordsRamipril    Extracellular signal-regulated kinase 1/2    Gap junction protein 43    Spontaneously hypertensive rats
    
基金资助:新疆维吾尔自治区卫生计生委青年医学科技人才专项科研项目,(编号:WJWY-201810)
通讯作者: 魏 童   
引用本文:   
赵亮, 魏童. 雷米普利通过激活ERK1/2-Cx43信号通路降低SHR大鼠的血压[J]. 河北医学, 2022, 28(8): 1251-1255.
ZHAO Liang, WEI Tong. Ramipril Reduces Blood Pressure in SHR Rats by Activating ERK1/2-Cx43 Signaling Pathway. HeBei Med, 2022, 28(8): 1251-1255.
链接本文:  
http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2022.08.04     或     http://www.hbyxzzs.cn/CN/Y2022/V28/I8/1251
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