黄芪总皂苷对缺氧性肺动脉高压作用探讨

目的　探讨黄芪总皂苷（AST）对缺氧性肺动脉高压（HPH）病理进展的抑制作用及相关机制。方法　28只SPF级雄性SD大鼠随机分为对照组、HPH组、HPH+AST15［15 mg/（kg·d）］组、HPH+AST45［45 mg/（kg·d）］组，每组7只。采用间断式常压低氧建立大鼠HPH模型。实验28 d后，检测大鼠右心室收缩压力（RVSP）；计算右心室（RV）和左心室+室间隔（LV+S）的比值RV/（LV+S）；HE染色及免疫荧光染色观察大鼠肺动脉结构重建，计算肺动脉厚度百分比（WT）、面积百分比（WA），并测量肺动脉α-平滑肌肌动蛋白（α-SMA）的光密度（OD）值；分光光度法检测大鼠肺组织及血清中的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）及丙二醛（MDA）水平；Western blot法检测大鼠肺组织中还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶Nox2和Nox4蛋白表达情况。结果　与对照组比较，HPH组大鼠RVSP、RV/（LV+S）、WT、WA、α-SMA均增高（P＜0.05），肺组织及血清中的SOD、CAT水平明显降低，而MDA水平增高（P＜0.05），肺组织中Nox2和Nox4蛋白表达水平升高（P＜0.05）。与HPH组比较，HPH+AST15组和HPH+AST45组大鼠RVSP、RV/（LV+S）、WT、WA、α-SMA均降低（P＜0.05），肺组织及血清中的SOD、CAT水平升高，MDA水平降低（P＜0.05），肺组织中Nox2和Nox4蛋白表达水平均降低（P＜0.05），其中HPH+AST45组WT、WA、α-SMA及肺组织MDA水平、Nox2和Nox4蛋白表达水平均较HPH+AST15组更低（P＜0.05）。结论　黄芪总皂苷可抑制大鼠HPH的病理进展，其机制可能与提高大鼠体内SOD和CAT水平并抑制Nox2和Nox4表达有关。

The potential effects of astragaloside on hypoxic pulmonary hypertension

Objective　To explore the inhibitory effect of astragaloside (AST) on the pathological development of hypoxic pulmonary hypertension (HPH) and its relevant mechanism. Methods　Twenty-eight SPF male Sprague-Dawley rats were randomly divided into 4 groups (7 rats per group): control group, HPH group, HPH+AST15 15 mg/(kg·d)] group, and HPH+AST45 45 mg/(kg·d)] group. The rat model of HPH was established by intermittent normal pressure hypoxia. After 28-day hypoxia exposure, the right ventricle systolic pressure (RVSP) and the weight ratio of RV/(LV+S) were recorded. After HE and immunofluorescence staining, the percent medial wall thickness (WT), percent medial wall area (WA), and integrated optical density (OD) value of α-smooth muscle actin (α-SMA) in pulmonary arteries were determined to investigate pulmonary artery structural remodeling. The content of SOD, CAT and MDA both in serum and in lung tissues were measured by spectrophotometry. The NADPH (reduced nicotinamide adenine dinucleotide phosphate) oxidase Nox2 and Nox4 protein expressions in lung tissues were detected by Western blot analysis. Results　 Compared with those in control group, the RVSP, RV/(LV+S) ratio, WT, WA, and α-SMA value were increased significantly in HPH group (P＜0.05), SOD and CAT levels both in serum and in lung tissues were decreased significantly in association with the elevated MDA content (P＜0.05), and the Nox2 and Nox4 protein levels in lung tissues were increased significantly (P＜0.05). However, compared with HPH group, the RVSP, RV/(LV+S) ratio, WT, WA, and α-SMA value were decreased significantly (P＜0.05), SOD and CAT levels both in serum and in lung tissues were increased significantly in association with the decreased MDA content (P＜0.05), and the Nox2 and Nox4 protein levels in lung tissues were significantly decreased (P＜0.05) in HPH+AST15 group and HPH+AST45 group. In addition, the WT, WA, α-SMA value, MDA level in lung tissues, and Nox2 and Nox4 protein levels in lung tissues were significantly decreased in HPH+AST45 group than those of the HPH+AST15 group (P＜0.05). Conclusion　AST can attenuate the pathological development of HPH in rats, which may be associated with the elevating levels of SOD and CAT and inhibiting the expressions of Nox2 and Nox4 in rats.