加味丹参饮对心肌纤维化模型大鼠心肌纤维化及Notch信号通路的影响  

Effect of Jiawei-Danshen Yin on anti-myocardial fibrosis and Notch signaling pathway in rats with myocardial fibrosis

作　　者：谭琦[1] 周小明[1] Tan Qi;Zhou Xiaoming(Department of Cardiology,the First Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410000,China)

机构地区：[1]湖南中医药大学第一附属医院心内科,长沙410000

出　　处：《国际中医中药杂志》2019年第9期964-968,共5页International Journal of Traditional Chinese Medicine

基　　金：中医内科学省部共建教育部重点实验室开放课题(2YNK201702)。

摘　　要：目的研究加味丹参饮对心肌纤维化模型大鼠抗心肌纤维化作用及对Notch信号通路的影响.方法将大鼠按随机数字表法分为正常组10只,模型组、拉托普利组、加味丹参饮低剂量组及加味丹参饮高剂量组各5只.除正常组外,其余各组大鼠制备心肌纤维化模型.造模后1 h,加味丹参饮低、高剂量组大鼠分别灌胃加味丹参饮1.5、3.0 mg/ml,卡托普利组灌胃卡托普利混悬液1 mg/ml,模型组和正常组大鼠灌胃等体积生理盐水,1次/d,连续灌胃7 d.采用超声仪检测大鼠心率(heart rate,HR)、左心室收缩压(left ventricular systolic pressure,LVSP)、左心室舒张期末压(Left ventricular end diastolic pressure,LVEDP),采用胶原纤维染色观察心肌病理学改变,并测量心肌胶原容积分数(collagen volume fraction,CVF),计算左心室质量指数(left ventricular mass index,LVMI)、心脏质量指数(heart weight index,HWI),采用Western blot检测心肌组织Notch信号通路蛋白1(Notch1)、Notch胞内区域(Notch intracellular domain,NICD)、Notch3、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)蛋白表达.结果与模型组比较,加味丹参饮低、高剂量组LVMI[(2.26±0.01)mg/g、(1.48±0.03)mg/g比(2.86±0.06)mg/g]、CVF[(3.44±1.45)%、(2.62±1.43)%比(7.82±1.95)%]、HWI[(4.05±0.02)mg/g、(3.11±0.02)mg/g比(4.58±1.05)mg/g]水平降低(P<0.05),LVEDP[(10.16±2.35)kPa、(6.25±1.23)kPa比(13.15±3.06)kPa]水平降低,HR[(375.22±20.36)次/min、(450.32±22.13)次/min比(329.36±22.01)次/min]、LVSP[(90.12±6.32)kPa、(110.45±10.71)kPa比(80.54±10.35)kPa]水平升高(P<0.05),心肌组织Notch1[(0.83±0.05)、(1.11±0.04)比(0.51±0.06)]、NICD[(0.72±0.01)、(1.06±0.03)比(0.35±0.05)]、Notch3[(0.62±0.03)、(1.20±0.06)比(0.39±0.05)]蛋白表达升高,α-SMA[(1.12±0.08)、(0.92±0.05)比(1.43±0.07)]蛋白表达降低(P<0.05).结论加味丹参饮可改善心肌纤维化模型大鼠心肌纤维化,通过激活Notch信号通路,提高抗心肌纤维化能力.Objective To study the effect of Jiawei-Danshen Yin on anti-myocardial fibrosis and Notch signaling pathway in rats with myocardial fibrosis. Methods The rats were randomly divided into normal group (10 rats), model group (5 rats), latopril group (5 rats), low dose group (5 rats) and high dose group (5 rats). In addition to the normal group, the other groups of rats prepared myocardial fibrosis model. One hour after model establishment, the rats in high and low dosage groups were given 1.5 mg/ml and 3.0 mg/ml of modified salvia miltiorrhiza drink respectively, the rats in captopril group were given 1 mg/ml of captopril, the rats in model group and normal group were given saline of equal volume for 1 day/time for one week. The collagen volume fraction (CVF) was measured by pathological observation. The left ventricular mass index (LVMI), heart mass index (HWI), heart rate (HR), left ventricular systolic pre-existing (LVSP) left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure were measured. Western blot was used to detect the expression of Notch1, NICD, Notch3 and α-SMA. Results Compared with the model group, the levels of LVMI (2.26 ± 0.01 mg/g, 1.48 ± 0.03 mg/g vs. 2.86 ± 0.06 mg/g), CVF (3.44% ± 1.45%, 2.62% ± 1.43% vs. 7.82% ± 1.95%), HWI (4.05 ± 0.02 mg/g, 3.11 ± 0.02 mg/g vs. 4.58 ± 1.05 mg/g) in the low and high dose groups of Jiawei-Danshen Yin significantly decreased respectively(P<0.05). The levels of LVEDP (10.16 ± 2.35 kPa, 6.25 ± 1.23 kPa vs. 13.15 ± 3.06 kPa) significantly decreased, HR (375.22 ± 20.36 time/min, 450.32 ± 22.13 time/min vs. 329.36 ± 22.01 time/min), LVSP (90.12 ± 6.32 kPa, 110.45 ± 10.71 kPa vs. 80.54 ± 10.35 kPa) significantly increased (P<0.05) respectively. The expression of Notch1 (0.83 ± 0.05, 1.11 ± 0.04 vs. 0.51 ± 0.06), NICD (0.72 ± 0.01, 1.06 ± 0.03 vs. 0.35 ± 0.05), Notch3 (0.62 ± 0.03, 1.20 ± 0.06 vs. 0.39 ± 0.05) in myocardial tissue significantly increased, and the expression of α-SMA (1.12 ± 0.08, 0.92 ± 0.0

关 键 词：纤维化 心肌 加味丹参饮 NOTCH信号通路 心功能 大鼠 

分 类 号：R54[医药卫生—心血管疾病]