黄连解毒汤对自发性高血压大鼠主动脉组织miR-133a/Caveolin-1/eNOS通路调控作用机制的研究  

Study of Huanglian Jiedu Decoction on the regulation mechanism of the aortic tissue miR-133a/Caveolin-1/eNOS pathway in spontaneously hypertensive rats

作　　者：马晓聪[1] 熊兴江[2] 蔡涛[1] 黄婕 张爱珍[3] 岳桂华 MA Xiao-cong;XIONG Xing-jiang;CAI Tao;HUANG Jie;ZHANG Ai-zhen;YUE Gui-hua(Guangxi University of Chinese Medicine,Nanning 530020,China;Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530011,China;Guangxi Medical College,Nanning 530023,China)

机构地区：[1]广西中医药大学,南宁530020 [2]中国中医科学院广安门医院,北京100053 [3]广西中医药大学附属瑞康医院,南宁530011 [4]广西卫生职业技术学院,南宁530023

出　　处：《中华中医药杂志》2020年第8期3868-3872,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81560757,No.81860831)。

摘　　要：目的:探讨黄连解毒汤对自发性高血压大鼠(SHR)主动脉组织miR-133a/Caveolin-1/eNOS通路关键因子表达的影响。方法:SHR随机分为模型组,卡托普利组,黄连解毒汤低、中、高剂量组,WKY大鼠作为正常组,每组各10只。给予相应药物灌胃后,检测各组大鼠血清NO、内皮素-1(ET-1)及主动脉eNOS变化,RTPCR检测大鼠主动脉组织miR133a、Caveolin-1、eNOS mRNA表达,Western Blot检测大鼠主动脉组织Caveolin-1、eNOS、p-eNOS蛋白表达。结果:与正常组比较,模型组大鼠血清NO、主动脉eNOS含量显著降低(P<0.01),血清ET-1含量显著升高(P<0.01),模型组大鼠主动脉miR-133a、eNOS mRNA表达显著降低(P<0.01),主动脉Caveolin-1 mRNA和蛋白表达显著升高(P<0.01),主动脉eNOS、p-eNOS蛋白表达显著降低(P<0.01)。与模型组比较,各治疗组大鼠血清中NO、主动脉eNOS的含量不同程度升高,血清ET-1的含量不同程度降低。卡托普利组及黄连解毒汤中、高剂量组大鼠主动脉miR-133a、eNOS mRNA表达显著升高(P<0.01),Caveolin-1 mRNA和蛋白表达显著降低(P<0.01),eNOS、p-eNOS表达水平显著升高(P<0.01)。结论:黄连解毒汤可通过升高SHR主动脉miR-133a、eNOS mRNA表达水平及eNOS、p-eNOS蛋白的表达水平,降低Caveolin-1 mRNA及蛋白表达水平保护SHR大鼠血管内皮功能,达到降低血压的作用。Objective:To investigate the effects of Huanglian Jiedu Decoction(HLJDD)on the expression of key molecules of miR-133a/caveolin-1/eNOS pathway in the aorta of spontaneously hypertensive rats(SHR).Methods:SHR was randomly divided into model group,captopril group,HLJDD low,medium and high dose group,WKY rats as normal group,10 rats in each group.After gavage of corresponding drugs,the changes of serum NO,ET-1 and aortic eNOS were detected.The m RNA expressions of miR133a,Caveolin-1 and eNOS were detected by RT-PCR,the protein expressions of Caveolin-1,eNOS and p-eNOS were detected by Western Blot.Results:Compared with the control group,the model group’s levels of NO in serum and eNOS in aorta decreased significantly(P<0.01),the levels of ET-1 in serum increased significantly(P<0.01),the expression of miR-133a and eNOS mRNA decreased significantly(P<0.01),and the expression of Caveolin-1 mRNA and protein increased significantly(P<0.01),and the expression of eNOS and p-eNOS protein decreased significantly(P<0.01).Compared with the model group,the levels of NO and eNOS in serum and aorta were significantly increased in each treatment group,the levels of ET-1 in serum decreased significantly,the expressions of miR-133a and eNOS mRNA in aorta of rats in captopril group,HLJDD medium and high dose group were significantly higher(P<0.01),and the expression of Caveolin-1 mRNA and protein in aorta of rats in captopril group,HLJDD medium and high dose group was significantly lower(P<0.01),and the expressions of eNOS and p-eNOS in aorta in captopril group,HLJDD medium and high dose group were significantly higher(P<0.01).Conclusion:HLJDD can increasing the expression levels of miR-133a,eNOS mRNA,eNOS,p-eNOS protein expression,decreased the Caveolin-1 mRNA and protein expression,while protect vascular endothelial function and lower blood pressure of SHR.

关 键 词：黄连解毒汤 自发性高血压大鼠 内皮功能 miR-133a CAVEOLIN-1 

分 类 号：R285.5[医药卫生—中药学]