|
| 靶向纳米载体包封西地那非对肺高压大鼠肺血管重构的影响 |
| Effect of targeted nanoparticles embedded with sildenafil on the vascular remodeling in rats with pulmonary arterial hypertension |
| |
| DOI：10.12089/jca.2018.12.018 |
| 中文关键词: 肺动脉高压 纳米载体 西地那非 |
| 英文关键词: Pulmonary arterial hypertension Nanoparticles Sildenafil |
| 基金项目:国家自然科学基金(81470242);江苏省六大人才高峰(2016-WSN-147)；南京市卫生青年人才培养工程（QRX17013） |
|
| 摘要点击次数: 2838 |
| 全文下载次数: 1063 |
| 中文摘要: |
目的 观察包封西地那非的靶向纳米载体对野百合碱肺高压大鼠肺动脉压力、肺小血管中膜增殖以及右心室心肌肥厚的治疗作用。
方法 雄性SD大鼠42只,随机分为六组，每组7只。除对照组(CON组)外,其余各组皮下注射野百合碱60 mg/kg,4周后分别经尾静脉注射西地那非8 mg/kg(SIL组)、靶向纳米空载体(GL组)、普通纳米载体包封西地那非(L-SIL组)和靶向纳米载体包封西地那非(GL-SIL组)干预2周,CON组与模型组(MCT组)则给予等体积的生理盐水。2周后,开胸测量大鼠平均肺动脉压(mPAP)并处死动物取心肺组织,进行HE染色,测定肺小血管中膜厚度比例（WT）,右心室心肌细胞的面积。采用免疫组织化学法检测肺血管中膜α-平滑肌肌动蛋白(α-SMA)含量。采用活体荧光示踪观察靶向纳米载体的组织分布。
结果 与CON组比较,MCT组、GL组、SIL组和L-SIL组mPAP明显升高(P<0.05)。与MCT组比较,GL-SIL组mPAP明显降低(P<0.05)。与CON组比较,MCT组、SIL组、GL组和L-SIL组WT明显增加(P<0.05),α-SMA表达明显增高(P<0.05)。与MCT组比较，GL-SIL组WT和α-SMA的表达明显降低(P<0.05)。与CON组比较,MCT组、SIL组、GL组和L-SIL组心肌细胞面积明显增大(P<0.05)。但GL-SIL组明显小于MCT组(P<0.05)。
结论 靶向纳米载体包封西地那非可明显降低肺动脉高压大鼠的平均肺动脉压力,改善肺血管中膜增殖和右心室肥大,与其具有良好的肺组织靶向性相关。 |
| 英文摘要: |
Objective To explore the possible efficacy of glucose modified nanoparticles embedded with sildenafil on amelioration of pulmonary hypertension and pulmonary vascular remodeling in rats treated with monocrotaline.
Methods Forty-two male Sprague-Dawley rats were randomly divided into 6 groups with 7 rats for each group. All rats, except in Control group (group CON), were subjected to 60 mg/kg monocrotaline subcutaneous injection. After 4 weeks MCT insult, the rats received intravenous injection of sildenafil 8 mg/kg (group SIL), glucose modified nanoparticles (group GL),conventional nanoparticles embedded with sildenafil (group L-SIL), glucose modifiednanoparticles embedded with sildenafil (group GL-SIL) every other day for 2 weeks. The same volume of normal saline was substituted for drugs in the groups CON and MCT. The right lower lobes of the lungs were fixed in neutralformaldehyde for morphometric analysis and assessment of the medial thickness of pulmonary arterioles wall.The expressions of α-smooth muscle actin (α-SMA) were detected with immunohistochemistry assay. The cardiomyocyte volume of right ventricle was also measured under the high-resolution microscope. Ex vivo fluorescence imaging of DiR-loaded nanoparticles in the main tissues collected from rats at 4 h after intravenous injection.
Results Compared with group CON, the mPAP, WT, expressions of α-SMA and cardiomyocyte volume of right ventricle in groups MCT, SIL, GL and L-SIL were significantly increased (P < 0.05). Compared with group MCT, the mPAP, WT, expressions of α-SMA and cardiomyocyte volume of right ventricle in group GL-SIL were significantly reduced (P<0.05). The intensity of fluorescent of lung tissue was higher in DiR-loaded glucose modified nanoparticles compared with conventional nanoparticles after 4 h injection.
Conclusion Glucose modified nanoparticles embedded sildenafil can effectively inhibit the increase in mPAP, percentage of medial thickening and cardiomyocyte hypertrophy of right ventricle induced by MCT in rats, which might be associated with high affinity to lung of targeted nanoparticles and high efficiency drug-delivery system. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
