[1]陈莲,李冰冰.紫杉醇对肺高压大鼠血管重构及周围炎症的影响[J].徐州医科大学学报,2020,40(04):240-244.
 Effects of paclitaxel on vascular remodeling and peripheral inflammation in rats with pulmonary hypertension[J].Journal of Xuzhou Medical University,2020,40(04):240-244.
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紫杉醇对肺高压大鼠血管重构及周围炎症的影响()
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《徐州医科大学学报》[ISSN:2096-3882/CN:32-1875/R]

卷:
40
期数:
2020年04期
页码:
240-244
栏目:
出版日期:
2020-04-25

文章信息/Info

Title:
Effects of paclitaxel on vascular remodeling and peripheral inflammation in rats with pulmonary hypertension
作者:
陈莲李冰冰
文献标志码:
A
摘要:
目的 探讨静脉注射不同剂量紫杉醇对肺高压大鼠肺动脉压力,肺血管重构的治疗作用及其可能的机制。方法 雄性SD大鼠(南京医科大学提供,220 -250 g)共20只,随机分成4组。除空白组(CON组)外,其余三组接受野百合碱(Monocrotaline 60 mg/kg)皮下注射。四周后,干预组分别经尾静脉注射紫杉醇(PTX)2 mg/kg或者3 mg/kg,间隔4天静脉给药(共给药3次)。CON组和模型组(MCT组)经尾静脉注射等量生理盐水。实验结束,经肺动脉穿刺连接监护仪测量肺动脉压力,测压后大鼠行安乐死,取心肺组织行HE染色,测定中膜增厚比例(WT%),评估淋巴滤泡结构。免疫组织化学法测定转录因子FoxO1,α-SMA(α-平滑肌肌动蛋白)的表达,分析血管外膜巨噬细胞表型。结果 与CON组比较,MCT组平均肺动脉压力(mPAP)明显升高(P<0.05)。PTX-2 治疗组mPAP较MCT组明显降低(P<0.05)。PTX-3组较低剂量PTX组(PTX-2)能进一步降低肺动脉压力(P<0.05)。与CON组比较,MCT组α-SMA表达和WT%明显增加(P<0.05)。PTX干预能显著降低血管中膜增厚和α-SMA表达(P<0.05),PTX-3组进一步改善肺血管中膜增厚(P<0.05)。MCT组大鼠肺组织FoxO1较对照组下降, PTX-2 组能上调FoxO1表达(P<0.05),PTX-3组上调FoxO1相对PTX-2组作用更加明显(P<0.05)。MCT干预后肺血管周围淋巴滤泡和CD163+表型巨噬细胞(M2)相对CON组明显增加(P<0.05),PTX干预能降低淋巴滤泡比和抑制M2肺巨噬细胞聚集(P<0.05)。结论 紫杉醇(3 mg/kg)可以显著降低肺高压大鼠肺动脉压力,降低肺血管中膜增厚,缓解肺血管周围炎症,有效治疗肺高压。
Abstract:
ob<x>jective To investigate the therapeutic effect of paclitaxel on the pulmonary vascular remodeling and perivascular inflammation and its possible underlying mechanism in pulmonary hypertension rats treated with monocrotaline (MCT). Material and methods 20 male Sprague-Dawley rats were randomly allocated into 4 groups with 5 rats in each group: control group, MCT group, paclitaxel interventional groups (group PTX-2 or PTX-3). The rats received subcutaneous injection of 60 mg/kg monocrotaline in MCT group and paclitaxel interventional groups, while the same volume of DMSO was injected instead of MCT in control group. 4 weeks following the MCT insult, the rats were subjected to intravenous administration of paclitaxel at 2 mg/kg or 3 mg/kg every other 3 days for 3 times in the 14-day observational period in group PTX-2 and group PTX-3 respectively, whereas the equal volume of normal saline were substituted of paclitaxel in MCT group. At the end of experiment, the rats were anesthetized to undergo left thoracotomy for the exposure of the right ventricle of rats. The pulmonary arterial pressure (PAP) was measured with a catheter inserted into pulmonary trunk connecting to the pressure transducer. The rats were euthanized by intravenous injection of 10% potassium chloride thereafter. The lung tissue was exercised and fixed in 10% neutral formaldehyde for vasculature morphological and perivascular inflammation assessment. The immunohistochemistry assay was used to evaluate the ex<x>pression of FoxO1, ɑ-smooth muscle actin in media tunica of pulmonary arterioles. The macrophage surface marker of CD163 was applied to identify the phenotype of interstitial macrophages. Results Compared with control rats, MCT insult caused significant rise in mean PAP, percentage of media tunica thickening, the ratio of lymphoid follicles on Day 21. The decrease of mean PAP, the attenuation of medial tunica thickening or the ratio of lymphoid follicles was observed in PTX-2 group, moreover, the higher dose of PTX (3 mg/kg) was identified to be more effective in decrease of mean PAP, the attenuation of medial tunica thickening or the ratio of lymphoid follicles compared with PTX at dose of 2 mg/kg (P<0.05). The ex<x>pression of CD163 on macrophages was significantly increased in MCT group compared with Con group, the rescue of PTX significantly repress the accumulation of perivascular macrophages and the polarization to M2 macrophages. The ex<x>pression of FoxO1 was significantly decreased in MCT group compared with Con group. The intervention of PTX the accumulation of FoxO1, whereas, the higher dose of PTX (3 mg/kg) was identified to be more effective in increase of FoxO1. Conclusion paclitaxel elicits the therapeutic effect on pulmonary vascular remodeling and decreases the pulmonary arterial pressure, which is associated with upregulation of FoxO1 ex<x>pression and inhibition of M2 macrophages accumulation in the perivascular areas of lung interstitium.
更新日期/Last Update: 2020-05-08