神经药理学报 ›› 2017, Vol. 7 ›› Issue (3): 61-61.
• 2017年全国老年痴呆与认知障碍相关疾病学术会议论文摘要—认知障碍及其他疾病相关研究 • 上一篇 下一篇
Yeli Li, Yuting Wu, Yun Yue, Shu Fu, Danli Yang*
摘要: Objective:To investigate the effects of Osthole(Ost) on the right ventricle remodeling in monocrotaline-treated rats, and to explore the mechanisms. Methods:200~220g male Sprague-Dawley rats were randomly divided into normal control group (Control, n=8), model group (Model, n=8), low dose of Ost treatment group (Ost-L, 10 mg•kg-1, n=8), high dose of Ost treatment group (Ost-H, 20 mg•kg-1, n=8) and sildenafil treatment group (Sildenafil, 25 mg•kg-1, n=8).All rats were given a single dose of MCT 50 mg•kg-1 subcutaneously to establish the right ventricle remodeling except normal control group. Then the rats in the Ost and sildenafil treatment group were gavaged once daily from 1 day to 28 days. The other rats in the model group and normal control group were given the same amount of ddH2Owith 0.5% tween 80. After 28 days of administration, the right ventricular pressure were measured by right heart catheterization. Right ventricle(RV)and left ventricle plus septum(LV+SEP)were weighed separately. RV hypertrophy index (RVHI) were measured by the relative weight ratio of RV to LV+SEP. The morphological change of the RV were executed by light microscope and transmission electron microscope.The cardiomyocytes apoptosis were detected by TdT mediated nick dUTP end-labeling (TUNEL) method using the paraffin-embedded right ventricular tissues. The mRNA expression of Bcl-2, Bok and p53 were examined by real time RT-PCR. The protein expression of Bcl-2, Bax, Bok, IκB, IL-6, TNF-αand the levels of Cleaved caspase 3, p-NF-κB(p65) were detected by western blotting. Results:Compared with the control group, the right ventricular pressure and RVHI were increased obviously (P<0.05), myocardial hypertrophy, structure disorders, mitochondrial swelling and cardiomyocytes apoptosis (P<0.05)were observed in model group. The mRNA expression of Bok and p53 in right ventricular tissues were up-regulated (P<0.05), and the mRNA expression of Bcl-2 was down-regulated in model group (P<0.05).The protein expression of Bax, Bok, IL-6, TNF-αand the levels of Cleaved caspase 3, p-NF-κB(p65) were up-regulated (P<0.05), and the protein expression of Bcl-2 and IκBwere down-regulated significantly in model group (P<0.05). Compared with the model group, the right ventricular pressure and RVHI were decreased (P<0.05), myocardial hypertrophy, structure disorders, mitochondrial swelling and cardiomyocytes apoptosis (P<0.05) were improved significantly in Ost and sildenafil treatment group. The mRNA expression of Bok and p53 were down-regulated (P<0.05), while the mRNA expression of Bcl-2 was up-regulated (P<0.05) in Ost and sildenafil treatment group. The protein expression of Bax, Bok, IL-6, TNF-α, and the levels of Cleaved caspase 3, p-NF-κB(p65) were down-regulated (P<0.05), and the protein expression of Bcl-2 and IκBwere up-regulated significantly in Ost and sildenafil treatment group (P<0.05).Conclusions:Ost can resist the RV remodeling induced by MCT in rats, which may be related to these possible mechanisms: (1) Ost inhibits cardiomyocytes apoptosis by regulating Bax/Bcl-2 pathways; (2) Ost attenuates inflammation by inhibiting NF-κB pathway.