葛根素对缺氧性肺动脉高压及伴随的肺纤维化的作用

Effect of puerarin on hypoxic pulmonary hypertension and accompanying pulmonary fibrosis

探讨葛根素对由于缺氧导致的肺动脉高压及可能伴随的肺纤维化具有治疗的作用以及调控机制。采用缺氧箱建立缺氧性肺动脉高压的大鼠模型和缺氧给药组的大鼠模型。饲养18只清洁级SD大鼠,随机分成正常对照组、模型组、缺氧＋给药组,每天各组造模前30 min进行腹腔注射,缺氧＋给药组注射葛根素注射液20 mg·kg-1,正常对照组和模型组注射等体积0.9%Na Cl溶液。正常对照组是在实验室正常的环境下培养,模型组、缺氧＋给药组于缺氧环境下培养21 d后进行观察大鼠缺氧的特征初步判断造模情况,然后通过小动物超声法、右心导管法和HE染色等实验方法证明造模成功并且葛根素对于SD大鼠由缺氧造成的肺动脉高压具有治疗作用。通过荧光定量PCR,Western blot和免疫荧光方法检测由缺氧导致肺纤维化相关蛋白的变化情况,发现在缺氧时给予葛根素治疗可以促进CD31,VE-cadherin的表达,抑制α-SMA,vimentin和fibronection的表达,即抑制血管壁增厚。葛根素对由缺氧导致的大鼠发生肺动脉高压及其伴随的肺纤维化都具有治疗作用。

To investigate the effect and regulatory mechanism of puerarin on pulmonary arterial hypertension due to hypoxia and the possible accompanying pulmonary fibrosis,The rat model of hypoxic pulmonary hypertension and the rat model of hypoxia were established. Totally 18 clean-grade SD rats were fed and randomly divided into normal control group,model group and hypoxia ＋ medicine group. Each group received intraperitoneal injection 30 min before modeling every day; hypoxia ＋ medicine group was injected with 20 mg·kg-1 puerarin. Normal control group and model group were injected with the equal volume of 0. 9% Na Cl solution. Normal control group was cultured under normal conditions in the laboratory,while model group and hypoxia ＋ medicine group were cultured in ahypoxia environment for 21 days to observe rat hypoxic characteristics and make the preliminary judgment about modeling. Afterwards,small animal echocardiography,right cardiac catheterization,HE dyeing and other experiments were used to verify the successful modeling,and puerarin has a therapeutic effect in pulmonary hypertension caused by hypoxia in SD rats. Fluorescence quantitative PCR,Western blot and immunofluorescence method were used to detect the changes caused by hypoxia pulmonary fibrosis-associated protein.It was found that puerarin could be given in anoxia to promote the expressions of CD31,VE-cadherin,inhibit the expressions ofα-SMA,vimentin and fibronection,namely the inhibition of vascular wall thickening. Puerarin has the therapeutic effect on the pulmonary hypertension and accompanying pulmonary fibrosis in rats induced by hypoxia.