目的 研究酒石酸美托洛爾通過調(diào)節(jié)轉(zhuǎn)化生長(zhǎng)因子-β（TGF-β）/Smad信號(hào)通路抑制大鼠胸主動(dòng)脈瘤（TAA）進(jìn)程的分子機(jī)制。方法 暴露大鼠胸降主動(dòng)脈1 cm，將已用0.5 mol/L的氯化鈣浸泡好的棉紗覆蓋血管外膜15~20 min，建立TAA模型，設(shè)置模型組和酒石酸美托洛爾高、中、低劑量（0.60、0.30、0.15 mg/kg）組，另取10只大鼠作為對(duì)照組，每天1次，連續(xù)ig給藥4周，模型組和對(duì)照組ig等體積蒸餾水。對(duì)大鼠生理活動(dòng)進(jìn)行觀察和記錄，HE染色觀察動(dòng)脈管腔面改變；實(shí)時(shí)熒光定量PCR （qRT-PCR）和Western blotting對(duì)大鼠TAA組織中的TGF-β、Smad2、Smad3的表達(dá)水平進(jìn)行檢測(cè)。結(jié)果 與對(duì)照組比較，模型組大鼠進(jìn)食較少，體質(zhì)量減輕，精神萎靡，毛發(fā)雜亂，無(wú)光澤，活動(dòng)減少；酒石酸美托洛爾組與模型組比較，生理狀態(tài)好轉(zhuǎn)；HE染色顯示，對(duì)照組主動(dòng)脈壁彈力板排列規(guī)則、緊密，呈波浪形膜狀；模型組動(dòng)脈瘤壁的彈力板平直，并且有斷裂現(xiàn)象；與模型組比較，酒石酸美托洛爾組彈力板斷裂減少，動(dòng)脈壁呈波浪形膜狀。與對(duì)照組比較，模型組瘤組織中的TGF-β、Smad2、Smad3的mRNA、蛋白表達(dá)水平均顯著上調(diào)（P<0.05）；與模型組織比較，酒石酸美托洛爾組TGF-β、Smad2、Smad3的mRNA、蛋白表達(dá)水平均顯著下調(diào)（P<0.05），且呈劑量相關(guān)性。結(jié)論 酒石酸美托洛爾通過調(diào)節(jié)TGF-β/Smad信號(hào)通路抑制大鼠TAA的進(jìn)程。

Objective To investigate metoprolol tartrate regulated TGF-β/Smad signal pathway suppressed thoracic aortic aneurysms progression. Methods After exposing the descending thoracic aorta of rats for 1 cm, the cotton yarn immersed in 0.5 mol/L calcium chloride was covered with adventitia for 15~20 minutes to establish TAA model. The model group, the high, medium and low dose of metoprolol tartrate (0.60, 0.30, 0.15 mg/kg) group were set up, another 10 rats were taken as control group. Corresponding drugs was ig administered once a day for four weeks, distilled water was ig administered in model group and control group. The physiological activities of rats were observed and recorded, HE staining was used to observe the changes of arterial lumen surface. TGF-β, Smad2, Smad3 mRNA detected by real time PCR, and TGF-β, Smad2, Smad3 protein level analyzed by western blotting. Results Compared with control group, rats in model group ate less, had lighter body weight, mental retardation, disordered hair, no luster and less activity; compared with model group, the physiological state of the rats in the metoprolol tartrate group improved. HE staining showed that the elastic plates in the aortic wall of the control group were arranged regularly and tightly in a wavy membrane shape; the elastic plates in the aneurysm wall of the model group were straight and fractured; compared with the model group, the elastic plates in the metoprolol tartrate group were less fractured and the arterial wall was wavy membrane shape. Compared with the control group, the expression levels of TGF-β, Smad2 and Smad3 in model group were significantly increased (P<0.05); compared with model group, the expression levels of TGF-β, Smad2 and Smad3 in the metoprolol tartrate group were significantly decreased (P<0.05), and there was a dose-dependent relationship. Conclusion metoprolol regulated TGF-β/Smad signal pathway suppressed thoracic aortic aneurysms progression.