环孢菌素A对大鼠血压的影响  

Effect of cyclosporine A on blood pressure in rats

作　　者：张盼 韩莉花 王婷 王钰莹 史永恒[1] 刘继平[1] 刘维海 王川 ZHANG Pan;HAN Li-hua;WANG Ting;WANG Yu-ying;SHI Yong-heng;LIU Ji-ping;LIU Wei-hai;WANG Chuan(College of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi Province,China;Department of Pharmacy,Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi Province,China)

机构地区：[1]陕西中医药大学药学院,陕西咸阳712046 [2]陕西中医药大学附属医院药剂科,陕西咸阳712000

出　　处：《中国临床药理学杂志》2023年第11期1557-1561,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学青年科学基金资助项目(81800401);陕西省教育厅一般专项基金资助项目(22JK0348);陕西省科技厅一般基金资助项目(2022SF-207);陕西中医药大学附属医院院级基金资助项目(2020MS019)。

摘　　要：目的研究环孢菌素A(CsA)对大鼠血压的影响及机制。方法用离体血管环技术研究CsA对5-羟色胺(5-HT)受体介导的肠系膜动脉平滑肌收缩功能的影响,用蛋白质印迹法检测5-羟色胺受体以及5′-腺嘌呤核苷酸依赖的蛋白激酶和丝裂原活化蛋白激酶(AMPK/MAPK)信号通路相关蛋白的表达水平。将SD大鼠随机分为3组:正常对照组、CsA 15 mg·kg^(-1)组和CsA 25 mg·kg^(-1)组,CsA组皮下注射不同剂量的CsA,每天1次,连续21 d,正常对照组皮下注射等体积大豆油。每周测量大鼠的收缩压与舒张压。给药3周后,用离体血管环技术观察动脉收缩量效曲线的变化,用蛋白质印迹法检测5-羟色胺受体蛋白的表达水平。结果CsA可以增强5-羟色胺引起的血管收缩并使5-羟色胺受体蛋白的表达增加,AMPK通路激活剂AICAR和MAPK通路抑制药U0126、SP600125、SB203580可以抑制环孢菌素A诱导的血管收缩反应并降低5-羟色胺受体以及p-ERK1/2、p-JNK1/2、p-P38蛋白的表达。动物实验结果表明,皮下注射CsA 3周后,正常对照组、CsA 15 mg·kg^(-1)和CsA 25 mg·kg^(-1)组的收缩压分别为(130.8±8.0)、(146.1±8.3)和(157.1±9.8)mmHg,舒张压分别为(87.9±9.9)、(100.4±8.4)和(105.6±11.3)mmHg;与正常对照组相比,CsA各剂量组的收缩压和舒张压均显著升高(均P<0.05)。CsA 25 mg·kg^(-1)组明显地增强了5-羟色胺介导的收缩反应。蛋白质印迹结果表明,对照组、CsA 15 mg·kg^(-1)和CsA 25 mg·kg^(-1)组的5-HT1B蛋白相对表达水平分别为1.00±0.08、1.28±0.10和1.55±0.15;CsA 25 mg·kg^(-1)组可使5-HT1B受体蛋白表达增多。结论CsA通过抑制AMPK通路和激活MAPK通路上调5-HT受体诱导的血管收缩。Objective To investigate the effect and mechanism of cyclosporine A(CsA)on blood pressure in rats.Methods The effect of CsA on 5-hydroxytryptamine-mediated smooth muscle contraction was studied in vitro vascular ring technique and detected 5-hydroxytryptamine receptor and 5′-monophosphate-activated protein kinase/mitogen-activated protein kinase(AMPK/MAPK)pathway related proteins expression by Western blotting.SD rats were divided into 3 groups:Control group,CsA 15 mg·kg^(-1) group and CsA 25 mg·kg^(-1) group.CsA groups were subcutaneously injected with different doses of CsA for 21 d,and control group was subcutaneously injected with equal volume of soybean oil.Systolic blood pressure and diastolic blood pressure were measured weekly.After three weeks administration,changes of dose-effect curve of arterial constriction were observed by in vitro vascular ring technique and Western blotting was used to detect the protein expression of 5-hydroxytryptamine receptor.Results CsA enhanced the vasoconstriction induced by 5-hydroxytryptamine and increased the expression of 5-hydroxytryptamine receptor.AMPK pathway activator AICAR and MAPK pathway inhibitors U0126,SP600125,SB203580 inhibited the vasoconstriction response and decreased the protein level of 5-hydroxytryptamine receptor and p-ERK1/2,p-JNK1/2,p-P38.The results of animal experiments showed that,the systolic blood pressure of control,CsA 15 mg·kg^(-1) and CsA 25 mg·kg^(-1) groups were(130.8±8.0),(146.1±8.3)and(157.1±9.8)mmHg after subcutaneous injection of CSA for 3 weeks;the diastolic blood pressure were(87.9±9.9),(100.4±8.4),(105.6±11.3)mmHg.Compared with control group,systolic blood pressure and diastolic blood pressure were increased in CsA groups(all P<0.05).CsA 25 mg·kg^(-1) significantly enhanced the 5-HT-mediated contraction response,and Western blotting results showed that 5-HT1B protein expression levels in control,CsA 15 mg·kg^(-1) and CsA 25 mg·kg^(-1) groups were 1.00±0.08,1.28±0.10,1.55±0.15.CsA 25 mg·kg^(-1) group can increase

关 键 词：环孢菌素A 肠系膜动脉 5-羟色胺受体 5′-腺嘌呤核苷酸依赖的蛋白激酶 丝裂原活化蛋白激酶 

分 类 号：R979.5[医药卫生—药品]