Wu Guo-Tai, Du Li-Dong, Chen Zhen-He, Lin Xing-Yao, Li Jin-Tian, Li Fang
Gansu University of Chinese Medicine, Key Laboratory of Dunhuang Medicine and Transformation in Ministry of Education, Lanzhou 730000, China.
Key Laboratory of Pharmacology and Toxicology of TCM in Gansu Province, Lanzhou 730000, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2017 Jun 8;33(6):558-563. doi: 10.12047/j.cjap.5601.2017.132.
To observe the therapeutic effects and mechanism of Dunhuang Liaofengxushouruo decoction (LXD) (Traditional Chinese Medicine) on chronic heart failure(CHF) in rats.
Forty-eight male Wistar rats were randomly divided into normal group(=8):model group, captopril group and LXD(Traditional Chinese Medicine) high, medium and low dose group. Except the normal group, the rats were intravenous injected with adriamycin 2.5 mg/kg in one day for 6 weeks, the captopril rats were intragastric administrated by captopril 25 mg/kg, LXD high, medium and low dose groups were intragastric administrated by LXD of 80, 40, 20 g/kg for 6 consecutive weeks. The rats breathing, coat color, activity, body weight(BW) and time of exhaustive swimming were measured; Heart rate, mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular pressure (+dp/dtmax or -dp/dtmax)of each rat were examined by Power Lab. The levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured; The rats were sacrificed and hearts removed for separation of left and right ventricle, the antioxidant activity and ventricular mass index were measured, left ventricular myocardium was administrated by 4% paraformaldehyde, HE staining, morphological changes were observed under microscope.
Body weight of each group decreased, and time of exhaustive swimming decreased after modeling (<0.01). At 28 days after administration, BW in high and middle dose of LXD groups were increased and the swimming time of rats in LXD high dose group was increased (<0.05).At 42 days, BW in all of LXD groups were increased and the exhaustive swimming time of high and middle dose of LXD were prolonged (<0.05), MAP was decreased and LVSP, +dp/dtmax or -dp/dtmax were increased in LXD high and middle groups. The LVEDP was decreased in high dose of LXD group(<0.05,<0.01). The levels of creatine kinase (CK) and aspartate aminotransferase (AST) in middle and low dose of LXD groups were decreased(<0.05,<0.01), and the serum levels of IL-6, TNF-α and malondialdehyde (MDA) in serum in LXD high and middle dose groups were lower. The activities of superoxide dismutase (SOD) in serum were increased in all of LXD groups, and the LVMI and RVMI were decreased in high and middle dose of LXD groups(<0.05,<0.01). The pathological results showed that myocardial fiber arrangement and myocardial interstitial edema phenomenon were obviously improved in high dose of LXD group and CMD decreased.
Therapeutic effect of LXD on CHF by doxorubicin-induced in rats is confirmed, the mechanisms are associated with improved hemodynamics and myocardial tissue.
观察敦煌疗风虚瘦弱方(LXD,中药)对大鼠慢性心力衰竭(CHF)的治疗作用及机制。
48只雄性Wistar大鼠随机分为正常组(n = 8)、模型组、卡托普利组和LXD(中药)高、中、低剂量组。除正常组外,其余大鼠连续6周每日静脉注射阿霉素2.5 mg/kg,卡托普利组大鼠灌胃给予卡托普利25 mg/kg,LXD高、中、低剂量组大鼠分别灌胃给予80、40、20 g/kg的LXD,连续6周。测量大鼠呼吸、毛色、活动、体重(BW)和力竭游泳时间;用Power Lab检测每只大鼠的心率、平均动脉压(MAP)、左心室收缩压(LVSP)、左心室舒张末期压力(LVEDP)、左心室压力最大变化速率(+dp/dtmax或-dp/dtmax)。检测白细胞介素-6(IL-6)和肿瘤坏死因子α(TNF-α)水平;处死大鼠,取出心脏分离左右心室,测量抗氧化活性和心室质量指数,左心室心肌用4%多聚甲醛固定,HE染色,显微镜下观察形态学变化。
建模后各组体重均下降,力竭游泳时间减少(P<0.01)。给药28天后,LXD高、中剂量组体重增加,LXD高剂量组大鼠游泳时间增加(P<0.05)。给药42天时,LXD各组体重均增加,LXD高、中剂量组力竭游泳时间延长(P<0.05),LXD高、中剂量组MAP降低,LVSP、+dp/dtmax或-dp/dtmax升高。LXD高剂量组LVEDP降低(P<0.05,P<0.01)。LXD中、低剂量组肌酸激酶(CK)和天冬氨酸转氨酶(AST)水平降低(P<0.05,P<0.01),LXD高、中剂量组血清中IL-6、TNF-α和丙二醛(MDA)水平降低。LXD各组血清中超氧化物歧化酶(SOD)活性升高,LXD高、中剂量组LVMI和RVMI降低(P<o.05,P<o.01)。病理结果显示,LXD高剂量组心肌纤维排列和心肌间质水肿现象明显改善,CMD降低。
证实LXD对阿霉素诱导的大鼠CHF有治疗作用,其机制与改善血流动力学和心肌组织有关。