红景天苷通过抑制氧化应激防治大鼠低氧性肺动脉高压

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(P0.05);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(P0.05)。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。

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

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 into 4 groups:normoxia (N) group, hypoxia for 4 weeks (H₄) group, low-dose salidroside (hypoxia for 4 weeks and treatment with salidroside at 16 mg/kg, H₄S16) group and high-dose salidroside (hypoxia for 4 weeks and treatment with salidroside at 32 mg/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 of 8-iso-prostaglandin F_2α (8-iso-PGF_2α) 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 oxidase 4 (NOX4) and SOD1 in the lung tissues was determined by Western blot. RESULTS: Compared with N group, the levels of mPAP, RV/(LV+S) and WA/TA in H₄ group were significantly increased, which were apparently attenuated by salidroside injection in a dose-dependent manner. Meanwhile, salidroside administration apparently decreased the levels of MDA and 8-iso-PGF_2α in the serum and lung tissues, as well as the expression of NOX4 in the lung tissues. Besides, compared with N group, the activity of SOD in the serum and the expression of SOD1 in the lung tissues in H₄ group were significantly decreased, while administration of salidroside increased the activity of SOD in the serum and the expression of SOD1 in 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.