红景天苷对野百合碱诱导肺动脉高压大鼠Nrf-2及NF-κB信号通路的影响

Effect of Salidroside on the Nrf-2 and NF-κB signal pathway in monocrotaline-induced pulmonary hypertension in rats

目的:探讨红景天苷对肺动脉高压大鼠的肺组织病理与Nrf-2及NF-κB信号通路的影响。方法:将6~8周龄雄性SD大鼠随机分为五组,每组6只。正常对照组注射对照溶剂,模型对照组及药物干预组(低、中、高)皮下注射60mg/kg野百合碱后,于2~28d后分别给予低、中、高浓度组注射50、100、200mg/(kg·d)红景天苷,其余组别分别注射生理盐水;实验结束后,分别检测各组大鼠右心室收缩压(RVSP)及右心室肥厚指数;组织病理学检测大鼠肺组织细小动脉病理变化,RT-PCR检测肺组织HO-1、TNF-α、IL-6mRNA表达水平,Western blot检测肺组织核蛋白Nrf-2、NF-κB p65蛋白表达水平。结果:与正常对照组比较,模型对照组RVSP及右心室肥厚指数显著上升,肺组织表现明显炎症浸润,肺组织核蛋白Nrf-2及NF-κB均出现上调,HO-1及TNF-α、IL-6mRNA表达上调(P<0.05);经过不同浓度红景天苷干预后,各组大鼠RVSP及右心室肥厚指数出现变化,高浓度组显著下调(P<0.05);Nrf-2核蛋白水平及HO-1mRNA表达进一步上升,NF-κB p65水平及TNF-α、IL-6mRNA表达逐渐下调,呈浓度依赖(P<0.05)。结论:红景天苷能够减缓野百合碱诱导的大鼠肺动脉高压,可能与Nrf-2活化以及抑制NF-κB信号通路有关。

Objective ： To investigate the effect of salidroside on Nrf-2/NFκB signaling pathway on lung tissue pathology in rats with pulmonary hypertension. Methods： 6-8 week male SD rats were randomly divided into 5 groups, with 6 rats in each group. Normal control group was injected with control solvent, model control group and drug intervention group （low,middle,high） subcutaneous injection of 60 mg/kg monocrotaline. The low, medium and high concentration groups were given 50, 100 and 200 mg/（kg · d） of salidroside in 2-28 day. The other groups were injected with normal saline. At the end of the experiment, the right ventricular systolic pressure （RVSP） and the right ventricular hypertrophy index were detected in each group. Histopathological examination of the pathologi-cal changes of pulmonary tissue in rats. The mRNA expression level of HO-1, TNF-α, and IL-6 in lung tissue was detected by RT-PCR. The protein expression level of Nrf-2 and NF-κB p65 in lung tissue nuclear protein was detec-ted by Western blot. Results： Compared with the normal control group, the RVSP and the right ventricular hyper-trophy index of the model group increased significantly, and the lung tissue showed significant inflammatory infiltra-tion. The expression of Nrf-2 and NF-κB in lung tissue nuclear protein was up-regulated, and the expression of HO- 1 ,TNF, and IL6 mRNA was up-regulated （P 〈 0. 05）. After treatment with different concentrations of salidro-side ,RVSP and right ventricular hypertrophy index began to change, and which in the high concentration group was signifi-cantly decreased （P 〈0 . 05）. The level of Nrf-2 protein and the expression of HO-1 mRNA were further increased, the levels of NF-κB p65 and the expression of TNF-α and IL-6 mRNA were decreased gradually, and showed a concentration dependence （P 〈 0. 05）. Conclusion： Salidroside may alleviate the pulmonary hypertension induced by monocrotaline, which may be related to the activation of Nrf-2 and the inhibition of NF-κB signaling pathway.