钩藤生物碱对自发性高血压大鼠胸主动脉成纤维细胞凋亡/增殖及FN、LN的影响  

Effects of Rhynchophylla Alkaloids on Vascular Adventitial Fibroblast Apoptosis and Proliferation in the Thoracic Aorta of Spontaneously Hypertensive Rats

作　　者：戴国华[1] 孙敬昌[2] 齐冬梅[2] 周洪雷[2] 李运伦[1] 

机构地区：[1]山东中医药大学附属医院心内科,济南250011 [2]山东中医药大学,济南250355

出　　处：《中国中西医结合杂志》2012年第9期1233-1237,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.30300466);教育部新世纪优秀人才支持计划资助项目(No.NCET-07-0522);山东省自然科学基金资助项目(No.Y2006C99)

摘　　要：目的研究钩藤碱、异钩藤碱和钩藤总生物碱对自发性高血压大鼠(spontaneously hypertensive rat,SHR)胸主动脉血管外膜成纤维细胞(vascular adventitial fibroblasts,VAF)凋亡、增殖及Bcl-2、Bax、c-Fos、c-Myc、层黏连蛋白(laminin,LN)、纤维层黏连蛋白(fibronectin,FN)的影响。方法选择8周龄雄性SHR40只,随机分为模型组、卡托普利组(17.5mg/kg)、异钩藤碱组(5.0mg/kg)、钩藤碱组(5.0mg/kg)和钩藤总生物碱组(50.0mg/kg),每组8只。另选取8周龄雄性Wistar大鼠8只作为正常组。模型组和正常组灌胃给予等容量生理盐水。各组给药容积为每次10mL/kg,每周给药6天,连续8周,随体重变化调整给药量。采用AnnexinV-FITC结合PI染色、流式细胞术分析胸主动脉VAF凋亡率;免疫组化法检测胸主动脉VAFBcl-2、Bax、c-Myc、c-Fos、FN及LN蛋白表达;原位杂交法检测胸主动脉VAF转化生长因子-β1(transforming growth factor,TGF-β1)mRNA表达。结果与模型组比较,各用药组干预4、8周大鼠尾动脉收缩压均降低,胸主动脉VAF凋亡率、Bax蛋白均升高,Bcl-2、c-Fos、FN、LN蛋白及TGF-β1mRNA均降低,钩藤碱组、异钩藤碱组及钩藤总生物碱组c-Myc蛋白表达均降低,差异均有统计学意义(P<0.05,P<0.01)。与卡托普利组比较,钩藤碱组、异钩藤碱组及钩藤总生物碱组大鼠尾动脉收缩压、c-Fos蛋白表达及TGF-β1mRNA差异无统计学意义(P>0.05);胸主动脉VAF凋亡率升高,Bcl-2、c-Myc及LN蛋白表达均降低,差异均有统计学意义(P<0.05,P<0.01);钩藤碱组、异钩藤碱组Bax蛋白表达均升高,差异均有统计学意义(P<0.05,P<0.01);异钩藤碱组FN蛋白表达降低,差异有统计学意义(P<0.05)。钩藤碱组、异钩藤碱组及钩藤总生物碱组间比较,差异无统计学意义(P>0.05)。结论钩藤碱、异钩藤碱和钩藤总生物碱可能通过调节原癌基因Bcl-2和Bax蛋白表达,促进SHR胸主动脉VAF凋亡,通过下调c-Fos、c-Myc蛋白和TGF-β1mRNA表达途�Objective To study the effects of rhynchophylline, isorhynchophylline, and rhynchophylla alka- loids on the vascular adventitial fibroblasts （VAF） apoptosis and proliferation in thoracic aorta of spontaneously hy- pertensive rats （SHR）, and on the Bcl-2, Bax, c-Fos, c-Myc, laminin （LN）, and fibronectin （FN）. Methods For- ty 8-week old male SHR were randomly divided into five groups, i. e., the model group, the captopril group （17. 5 mg/kg）, the isorhynchophylline group （5. 0 mg/kg）, the rhynchophylline group （5. 0 mg/kg）, and the rhyn- chophylla alkaloids group （50. 0 mg/kg）, 8 in each group. In addition, eight 8-week old male Wistar rats were se- lected as the normal group. Equal volume of normal saline was given to rats in the normal group and the model group by gastrogavage. Rats in the rest groups were perfused with isovolumic medication solution （10 mL/kg）, six days per week for eight successive weeks. The dosage of drugs was adjusted according to the change of body weight. The VAF apoptosis rate of the thoracic aorta was measured by Annexin V-FITC combined with PI dyeing and flow cytometry. The protein expressions of thoracic aortic Bcl-2, Bax, c-Myc, c-Fos, FN, and LN were detec- ted by immunohistochemical assay. The adventitial transforming growth factor 131 （TGF-131） mRNA expression in the thoracic aorta was detected by in situ hybridization method. Results Compared with the model group, the tail arte- rial systolic pressure decreased, the VAF apoptosis and the protein expression of Bax increased, Bcl-2, c-Fos, FN, LN, and TGF-131 mRNA all decreased in the thoracic aorta of SHR in each treatment group after 4-and 8-week of intervention. Rhynchophylline, isorhynchophylline, and rhynchophylla alkaloids could inhibit the protein expres- sion of c-Myc with statistical difference （P 〈0. 05, P 〈0. 01 ）. Compared with the captopril group, there was no sta- tistical difference in decreasing the tail arterial systolic pressure, the protein expression of c-Fos and th

关 键 词：钩藤碱 异钩藤碱 钩藤总生物碱 自发性高血压 主动脉外膜成纤维细胞 凋亡/增殖 

分 类 号：R285.5[医药卫生—中药学]