摘要
目的：探讨黄芩苷对阿霉素（ADR）诱导扩张型心肌病大鼠心室重构、心室肌细胞凋亡及β_1肾上腺素受体（β_1-AR）/蛋白激酶A（PKA）/钙调素依赖蛋白激酶Ⅱ（CaMKⅡ）信号通路的影响。方法：雄性Wistar大鼠60只,随机分为正常组、模型组、黄芩苷低、中、高剂量组及卡维地洛组;模型组给予ADR 2 mg·kg^（-1）腹腔注射,黄芩苷组及卡维地洛组在模型组基础上分别给予黄芩苷（25,50,100 mg·kg^（-1）·d^（-1））,卡维地洛10 mg·kg^（-1）·d^（-1）灌胃,正常组给予等体积0.9%NaCl腹腔注射,1次/周,共3次;7周末各组大鼠行心脏超声检测心室变化及心功能指标;酶联免疫吸附法（ELISA）检测各组大鼠血清氨基末端脑钠肽前体（N-terminal pro-brain natriuretic peptide,NT-pro BNP）,人基裂解素（human stromelysin-2,ST2）含量;采用原位末端转移酶标记法（TUNEL）染色观察各组大鼠心室肌细胞凋亡情况;蛋白免疫印迹法（Western blot）检测各组大鼠心室肌组织中β_1-AR,PKA及CaMKⅡ表达。结果：与正常组比较,模型组大鼠出现心室重构明显及心功能减弱（P〈0.05）,血清NT-proBNP,ST2含量增多（P〈0.05）,心室肌细胞凋亡数量增加（P〈0.05）,心室肌组织中β_1-AR,PKA及CaMKⅡ表达增多;与模型组比较,黄芩苷及卡维地洛组大鼠心室重构及心功能改善（P〈0.05）,血清NT-pro BNP,ST2含量降低（P〈0.05）,心室肌凋亡数量减少（P〈0.05）,心室肌组织中β_1-AR,PKA及CaMKⅡ表达减少（P〈0.05）。结论：黄芩苷可有效改善ADR诱导的扩张型心肌病大鼠心室重构,减少心肌细胞凋亡,其机制可能与抑制心室肌细胞β-AR/PKA/CaMKⅡ信号通路表达有关。
Objective：To investigate the effects of baicalin on ventricular remodeling,ventricular myocyte apoptosis and β1-adrenoceptor（β1-AR）/protein kinase A（PKA）/Ca（2＋）/calmodulin-dependent priotein kinase Ⅱ（CaMK Ⅱ） signaling pathway in rats with dilated cardiomyopathy induced by adriamycin（ADR）.Method：Sixty male Wistar rats were randomly divided into normal group,model group,baicalin low,middle and high dose groups and Carvedilol group.The model group received intraperitoneal injection of ADR 2 mg·kg（-1）;Baicalin and Carvedilol groups were given with baicalin（25,50,100 mg·kg（-1））,carvedilol 10 mg·kg（-1）·d-1 gavage on the basis of model group; while the normal group was given with an equal volume of 0.9% Na Cl by intraperitoneal injection,1 time/week,for a total of 3 times.At the end of 7 weeks,the ventricular ultrasonography and heart function were measured by ultrasonography.The levels of N-terminal pro-brain natriuretic peptide（NT-proBNP） and human stromelysin-2（ST2） in serum were detected by enzyme-linked immunosorbent assay（ELISA）.The apoptosis of ventricular myocytes was observed by Td T-mediated d UTP nick-end labeling（TUNEL） staining.The expression levels of β1-AR,PKAand CaMK Ⅱ in ventricular myocytes were detected by Western blot.Result：As compared with the normal group,the rats in the model group showed obvious ventricular remodeling and decreased cardiac function（P 〈 0.05）; the levels of NT-pro BNP and ST2 were increased（P 0.05）; the number of apoptotic cells was increased（P 〈 0.05）,and the expression levels of β1-AR,PKA and CaMKⅡwere also increased.As compared with the model group,the ventricular remodeling and cardiac function were improved in baicalin and carvedilol groups; the levels of NT-pro BNP and ST2 were decreased（P 〈 0.05）,and the number of apoptotic cells was decreased（P 〈 0.05）; and the expression levels of β1-AR,PKA and CaMKⅡ in ventricular myocardium were also decreased（P 〈 0.05）.Conclusion：Baicalin can effectively improve the ventricular remodeling and decrease the apoptosis of cardiomyocytes in ADR-induced dilated cardiomyopathy rats.The mechanism may be related to the inhibition of β1-AR/PKA/CaMK Ⅱ signaling pathway in ventricular myocytes.
作者
王赛
胡烨
包斯图
WANG Sai;HU Ye;BAO Si-tu(Shengli Oil Field Central Hospital, Dongying 257000, China;Tongliao City Hospital, Tongliao 028000, China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2018年第9期140-144,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
内蒙古自然科学基金项目(2015MS08150)
