雷米普利通过激活ERK1/2-Cx43信号通路降低SHR大鼠的血压  

Ramipril Reduces Blood Pressure in SHR Rats by Activating ERK1/2-Cx43 Signaling Pathway

作　　者：赵亮[1] 魏童[1] ZHAO Liang;WEI Tong(The Fifth Affiliated Hospital of Xinjiang Medical University,Xinjiang Urumqi 830011,China)

机构地区：[1]新疆医科大学第五附属医院,新疆乌鲁木齐830011

出　　处：《河北医学》2022年第8期1251-1256,共6页Hebei Medicine

基　　金：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)。

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。Objective: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 kinase1/2(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-6rat 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-ERK1/2were 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.

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 

分 类 号：R965[医药卫生—药理学]