红景天苷通过抑制氧化应激防治大鼠低氧性肺动脉高压

Protective effect of salidroside on rats with hypoxic pulmonary hypertension by suppressing oxidative stress

目的:观察低氧性肺动脉高压大鼠肺组织及血清中氧化/抗氧化相关指标的变化,研究红景天苷(Sal)能否通过恢复氧化/抗氧化系统平衡防治低氧性肺动脉高压。方法:将32只SD大鼠随机分为4组:常氧(normoxia,N)组、低氧4周(hypoxia for 4 weeks,H_4)组、Sal低剂量(hypoxia for 4 weeks and treatment with Sal at 16mg/kg,H_4S16)组和Sal高剂量(hypoxia for 4 weeks and treatment with Sal at 32 mg/kg,H_4S32)组。造模完成后测定平均肺动脉压(m PAP)、右心室/(左心室+室间隔)[RV/(LV+S)]和血管壁面积/血管总面积(WA/TA);测量肺组织和血清中丙二醛(MDA)和8-异构前列腺素F_(2α)(8-iso-PGF_(2α))含量,并测量血清中超氧化物歧化酶(SOD)活性及肺组织中NADPH氧化酶(NOX4)和SOD1的相对表达量。结果:与N组相比,H_4组的NOX4相对表达量及MDA和8-iso-PGF_(2α)含量均显著升高(P<0.05);而与H4组相比,Sal低、高剂量组除m PAP、RV/(LV+S)和WA/TA明显减低外,NOX4的相对表达量及MDA和8-iso-PGF_(2α)含量亦明显减低(P<0.05)。与N组相比,H_4组的SOD1相对表达量和SOD活性显著下降,而Sal低、高剂量组的SOD1相对表达量和SOD活性均显著升高并呈剂量依赖性。结论:红景天苷可能通过减轻低氧引起的肺组织氧化应激损伤、恢复氧化/抗氧化系统平衡而起到改善肺动脉高压的作用。

AIM:To study whether salidroside plays a protective role in hypoxia-induced pulmonary hypertension by suppressing oxidative stress.METHODS:Sprague-Dawley rats were randomly divided into4groups:normoxia(N)group,hypoxia for4weeks(H4)group,low-dose salidroside(hypoxia for4weeks and treatment with salidroside at16mg/kg,H4S16)group and high-dose salidroside(hypoxia for4weeks and treatment with salidroside at32mg/kg,H4S32)group.The mean pulmonary arterial pressure(mPAP),the weight ratio of right ventricle/(left ventricle+septum)[RV/(LV+S)]and vessel wall area/vessel total area(WA/TA)were evaluated.The levels of malondialdehyde(MDA)in the serum and lung tissues were detected by colorimetric method.The levels of8-iso-prostaglandin F2α(8-iso-PGF2α)in the serum and lung tissues were measured by ELISA.The activity of superoxide dismutase(SOD)in the serum was analyzed by hydroxylamine method.The expression of NAPDH oxidase4(NOX4)and SOD1in the lung tissues was determined by Western blot.RESULTS:Compared with N group,the levels of mPAP,RV/(LV+S)and WA/TA in H4group were significantly increased,which were apparently attenuated by salidroside injection in a dose-dependent manner.Meanwhile,salidroside administration apparently decreased the levels of MDA and8-iso-PGF2αin the serum and lung tissues,as well as the expression of NOX4in the lung tissues.Besides,compared with N group,the activity of SOD in the serum and the expression of SOD1in the lung tissues in H4group were significantly decreased,while administration of salidroside increased the activity of SOD in the serum and the expression of SOD1in the lung tissues in a dose-dependent manner.CONCLUSION:Salidroside protects the pulmonary vessels from remodeling and attenuates hypoxia-induced pulmonary hypertension by inhibiting oxidative stress.