Lai Mei-Chih, Lin Jaung-Geng, Pai Pei-Ying, Lai Mei-Hsin, Lin Yueh-Min, Yeh Yu-Lan, Cheng Shiu-Min, Liu Yi-fan, Huang Chih-Yang, Lee Shin-Da
Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
Graduate Institute of Clinical Medical Science, China Medical University and Hospital, Taichung, Taiwan.
BMC Complement Altern Med. 2015 Jun 25;15:198. doi: 10.1186/s12906-015-0698-0.
The goal of this study is to determine if Rhodiola Crenulata (RC) has protective effects on mice hearts with severe sleep apnea model.
Sixty-four C57BL/6 J mice 5-6 months old were distributed into 4 groups i.e. Control group (21% O2, 24 h per day, 8 weeks, n=16); Hypoxia group (Hypoxia: 7% O2 60 s, 20% O2 alternating 60 s, 8 h per day, 8 weeks, n=16); Hypoxia+90RC and Hypoxia+270RC group (Hypoxia for 1st 4 weeks and hypoxia pretreated 90 mg/Kg and 270 mg/Kg Rhodiola Crenulata by oral gavage per day for 2nd 4 weeks, each n=16). Excised hearts from 4 groups of mice were analyzed for heart weight index changes using H&E staining, TUNEL-positive assays and Western Blotting protein.
Cardiac widely dispersed TUNEL-positive apoptotic cells in mice hearts were less in Hypoxia+RC90 and Hypoxia+RC270 than those in Hypoxia. Compared with Hypoxia, the protein levels of Fas ligand, Fas death receptors, Fas-Associated Death Domain (FADD), activated caspase 8, and activated caspase 3 (Fas dependent apoptotic pathways) were decreased in Hypoxia+RC90, Hypoxia+RC270. The protein levels of Bad, Bax, t-Bid, activated caspase 9, activated caspase 3 (mitochondria dependent apoptotic pathway) were less in Hypoxia+RC90, Hypoxia+RC270 than those in hypoxia. The protein levels of Bcl2, Bcl-xL, p-Bad (Bcl2-realted anti-apoptotic pathway) and VEGF, p-PI3k, p-AKT (VEGF-related pro-survival pathway) were higher in Hypoxia+RC90, Hypoxia+RC270 than those in hypoxia.
Our findings suggest that Rhodiola Crenulata have protective effects on chronic intermittent hypoxia-induced cardiac widely dispersed apoptosis via Fas-dependent and mitochondria-dependent apoptotic and VEGF-related pro-survival pathway.
本研究的目的是确定红景天(RC)对严重睡眠呼吸暂停模型小鼠心脏是否具有保护作用。
将64只5 - 6月龄的C57BL/6 J小鼠分为4组,即对照组(21%氧气,每天24小时,共8周,n = 16);缺氧组(缺氧:7%氧气60秒,交替20%氧气60秒,每天8小时,共8周,n = 16);缺氧+ 90RC组和缺氧+ 270RC组(前4周缺氧,后4周每天经口灌胃给予90毫克/千克和270毫克/千克红景天预处理,每组n = 16)。对4组小鼠的离体心脏进行分析,采用苏木精-伊红(H&E)染色、TUNEL阳性检测和蛋白质免疫印迹法检测心脏重量指数变化。
缺氧+ RC90组和缺氧+ RC270组小鼠心脏中广泛分布的TUNEL阳性凋亡细胞少于缺氧组。与缺氧组相比,缺氧+ RC90组、缺氧+ RC270组中Fas配体、Fas死亡受体、Fas相关死亡结构域(FADD)、活化的半胱天冬酶8和活化的半胱天冬酶3(Fas依赖性凋亡途径)的蛋白质水平降低。缺氧+ RC90组、缺氧+ RC270组中Bad、Bax、t - Bid、活化的半胱天冬酶9、活化的半胱天冬酶3(线粒体依赖性凋亡途径)的蛋白质水平低于缺氧组。缺氧+ RC90组、缺氧+ RC270组中Bcl2、Bcl - xL、p - Bad(Bcl2相关抗凋亡途径)和VEGF、p - PI3k、p - AKT(VEGF相关促生存途径)的蛋白质水平高于缺氧组。
我们的研究结果表明,红景天通过Fas依赖性和线粒体依赖性凋亡以及VEGF相关促生存途径,对慢性间歇性缺氧诱导的心脏广泛凋亡具有保护作用。