宋晓英.吡非尼酮通过调节急性心肌梗死大鼠TGF-β1/Smad通路改善心室重构[J].内科急危重症杂志,2021,27(6):505-510
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| DOI：10.11768/nkjwzzzz20210615 |
| 中文关键词: 吡非尼酮 TGF-β1/Smad通路 心肌梗死 心室重构 |
| 英文关键词: |
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| 中文摘要: |
| 摘要 目的：探讨吡非尼酮调节急性心肌梗死大鼠TGF-β1/Smad通路对心室重构的影响。方法：将72只SD大鼠随机分为假手术组、模型组、吡非尼酮低剂量组（50mg/kg）、吡非尼酮中剂量组(100mg/kg)、吡非尼酮高剂量组(200mg/kg)、福辛普利组（阳性对照组，15mg/kg），每组12只。除假手术组外，其余各组大鼠制备急性心肌梗死模型，药物处理组大鼠每天灌胃治疗，假手术组及模型组大鼠以同剂量生理盐水灌胃，持续14d，给药结束24h后，检测大鼠左心室质量指数；伊红（HE）、天狼星红染色分别检测大鼠心肌组织病理形态变化及心室纤维化程度；酶联免疫吸附法（ELISA）检测各组大鼠血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、转化生长因子β（TGF-β1)水平；免疫印迹实验（Western blot）检测各组大鼠心肌组织TGF-β1/Smad通路蛋白的表达情况。结果：与假手术组比较，模型组大鼠心肌组织形态改变明显，呈现心肌细胞肥大、坏死，心肌纤维扭曲、断裂，炎性细胞浸润等病理损伤，并有大量胶原沉积，呈现纤维化变性，左心室质量指数增大、血清TNF-α、IL-6及TGF-β1水平、心肌组织TGF-β1表达及p-Smad/Smad明显升高（P均＜0.05）。吡非尼酮低、中、高剂量组、福辛普利组大鼠病理损伤及纤维化程度较模型组轻，左心室质量指数、血清TNF-α、IL-6及TGF-β1水平、心肌组织TGF-β1表达及p-Smad/Smad较模型组降低，且吡非尼酮各组呈剂量依赖性（P均＜0.05）；吡非尼酮高剂量组与福辛普利组比较，差异无统计学意义（P>0.05）。结论：吡非尼酮可抑制心肌梗死大鼠心肌炎症，降低病理损伤及纤维化变性，改善心室重构，可能是通过下调TGF-β1/Smad通路实现的。 |
| 英文摘要: |
| Abstract Objective: To investigate the effect of pirfenidone on ventricular remodeling by regulating TGF-β1/Smad pathway in rats with acute myocardial infarction. Methods: Totally, 72 SD rats were randomly divided into sham operation group, model group, pirfenidone low-dose group (50mg/kg), pirfenidone medium-dose group (100mg/kg), pirfenidone high-dose group (200mg/kg) and fosinopril group (positive control group, 15mg/kg), with 12 rats in each group. Except for the sham operation group, rats in other groups were used to prepare acute myocardial infarction model. The animals in the drug treatment groups were treated by gavage every day, and those in sham operation group and model group were given the same dose of normal saline for 14d. At 24h after administration, the left ventricular mass index was measured. Eosin (HE) staining and Sirius red staining were used to detect the pathological changes of myocardial tissues and the degree of ventricular fibrosis. Serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and transforming growth factor β1 (TGF-β1) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of TGF-β1/Smad pathway proteins in myocardium of rats. Results: Compared with the sham operation group, the model group showed significantly morphological changes of myocardial tissue, including hypertrophy and necrosis of myocardial cells, distortion and fracture of myocardial fibers, inflammatory cell infiltration and other pathological damage, and a large amount of collagen deposition, presenting fibrosis degeneration. The levels of left ventricular mass index, the levels of TNF-α, IL-6 and TGF-β1 in serum, expression of TGF-β1 and p-smad/Smad in myocardial tissues were significantly increased (P<0.05). The pathological damage and fibrosis degree of pirfenidone low-dose, medium-dose and high-dose groups and fosinopril group were milder than those of model group. Compared with the model group, the levels of left ventricular mass index, levels of TNF-α, IL-6 and TGF-β1 in serum, the expression of TGF-β1 and p-smad/Smad were decreased in pirfenidone group in a dose-dependent manner (P<0.05). There was no significant difference between the high dose pirfenidone group and the fosinopril group (P>0.05). Conclusion: Pirfenidone can inhibit myocardial inflammation, reduce pathological damage and fibrosis, and improve the symptoms of ventricular remodeling in rats with myocardial infarction, which may be achieved by down-regulating TGF-β1/Smad pathway. |
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