Wan Lin-Feng, Yuan Zhi-Jun, Chen Hu
Department of Pharmacy,Yichun People's Hospital,Yichun,Jiangxi 336000,China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2022 Jun;44(3):384-391. doi: 10.3881/j.issn.1000-503X.14385.
Objective To investigate the effects of tea polyphenols on the renin-angiotensin-aldosterone system and the transforming growth factor-β1(TGF-β1)/Smads signaling pathway in heart failure rats.Methods SD rats were randomly assigned into a sham group,a model group,a captopril group(PC group),and a tea polyphenol group(TP group).The left anterior descending coronary artery was ligated with silk thread to establish the rat model of heart failure after myocardial infarction in the model group,PC group,and TP group,while it was not ligated in the sham group.Echocardiography was used to detect cardiac function.HE staining and Masson staining were conducted for the observation of myocardial pathological changes and myocardial fibrosis,respectively.Immunohistochemistry was employed to detect the expression of collagen Ⅰ and collagen Ⅲ.ELISA kits were used to measure the levels of angiotensin Ⅱ(AngⅡ),aldosterone(ALD),plasma renin activity(PRA),interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Western blotting was employed to determine the protein levels of TGF-β1,phosphorylated Smad2(p-Smad2),Smad2,p-Smad3,and Smad3.Results Compared with the sham group,the model group showed disordered myocardial cells with obvious inflammatory cell infiltration,increased degree of myocardial fibrosis(=9.748,=0.001),elevated levels of collagen Ⅰ(=11.754,=0.001) and collagen Ⅲ(=10.573,=0.001),decreased ejection fraction(EF)(=13.174,=0.002) and left ventricular short axis shortening rate(LVFS)(=11.853,=0.001),and up-regulated expression of AngⅡ(=4.246,=0.001),ALD(=5.385,=0.004),PRA(=4.386,=0.004),IL-1β(=4.393,=0.001),IL-6(=6.375,=0.002),and TNF-α(=4.753,=0.002),and up-regulated protein levels of TGF-β1(=6.365,=0.001),p-Smad2/Smad2(=13.755,=0.001),and p-Smad3/Smad3(=11.657,=0.002).Compared with the model group,PC and TP alleviated the myocardial pathological changes,decreased the left ventricular end-diastolic diameter(LVEDd)(=6.367,=0.003 and =5.264,=0.003),left ventricular end-systolic diameter(LVEDs)(=5.253,=0.002 and =5.974,=0.001),heart mass index(HMI)(=5.012,=0.007 and =4.953,=0.005),left ventricular mass index(LVMI)(=5.531,=0.003 and =5.483,=0.004),and the degree of myocardial fibrosis(=6.734,=0.001 and =5.362,=0.001).Furthermore,they lowered the levels of collagen Ⅰ (=5.373,=0.001 and =4.364,=0.001) and collagen Ⅲ(=6.764,=0.001 and =4.579,=0.001),increased EF(=11.264,=0.002 and =10.356,=0.001) and LVFS(=8.246,=0.002 and =7.824,=0.001),and down-regulated the expression of AngⅡ(=3.126,=0.001 and =2.853,=0.001),ALD(=3.854,=0.004 and =3.164,=0.004),PRA(=3.126,=0.004 and =3.063,=0.004),IL-1β(=2.964,=0.001 and =2.765,=0.001),IL-6(=4.865,=0.002 and =4.275,=0.002),and TNF-α(=3.146,=0.002 and =2.973,=0.002).In addition,they down-regulated the protein levels of TGF-β1(=4.657,=0.001 and =4.176,=0.001),p-Smad2/Smad2(=9.687,=0.001 and =6.753,=0.001) and p-Smad3/Smad3(=6.477,=0.002 and =4.754,=0.002).Conclusion Tea polyphenols protect rats from heart failure by inhibiting the activation of renin-angiotensin-aldosterone system and TGF-β1/Smads pathway.
目的 探讨茶多酚对心力衰竭大鼠肾素 - 血管紧张素 - 醛固酮系统及转化生长因子 -β1（TGF -β1）/Smads信号通路的影响。方法 将SD大鼠随机分为假手术组、模型组、卡托普利组（PC组）和茶多酚组（TP组）。模型组、PC组和TP组采用丝线结扎左冠状动脉前降支建立心肌梗死后心力衰竭大鼠模型，假手术组不结扎。采用超声心动图检测心功能。分别进行HE染色和Masson染色观察心肌病理变化和心肌纤维化。采用免疫组织化学检测Ⅰ型胶原和Ⅲ型胶原的表达。使用ELISA试剂盒检测血管紧张素Ⅱ（AngⅡ）、醛固酮（ALD）、血浆肾素活性（PRA）、白细胞介素 -1β（IL -1β）、IL -6和肿瘤坏死因子 -α（TNF -α）水平。采用Western blotting检测TGF -β1、磷酸化Smad2（p - Smad2）、Smad2、p - Smad3和Smad3的蛋白水平。结果 与假手术组相比，模型组心肌细胞排列紊乱，有明显炎性细胞浸润，心肌纤维化程度增加（ =9.748， =0.001），Ⅰ型胶原（ =11.754， =0.001）和Ⅲ型胶原（ =10.573， =0.001）水平升高，射血分数（EF）降低（ =,13.174， =0.002），左心室短轴缩短率（LVFS）降低（ =11.853， =0.001），AngⅡ（ =4.246， =0.001）、ALD（ =5.385， =0.004）、PRA（ =4.386， =0.004）、IL -1β（ =4.393， =0.001）、IL -6（ =6.375， =0.002）和TNF -α（ =4.753， =0.002）表达上调，TGF -β1（ =6.365， =0.001）、p - Smad2/Smad2（ =13.755， =0.001）和p - Smad3/Smad3（ =11.657， =0.002）蛋白水平上调。与模型组相比，PC组和TP组减轻了心肌病理变化，降低了左心室舒张末期内径（LVEDd）（ =6.367， =0.003和 =5.264， =0.003）、左心室收缩末期内径（LVEDs）（ =5.253， =0.002和 =5.974， =0.001）、心脏质量指数（HMI）（ =5.012， =0.007和 =4.95 <,sub>3， =0.005）、左心室质量指数（LVMI）（ =5.531， =0.003和 =5.483， =0.004）以及心肌纤维化程度（ =6.734， =0.001和 =5.362， =0.001）。此外，它们降低了Ⅰ型胶原（ =5.373， =0.001和 =4.364， =0.001）和Ⅲ型胶原（ =6.764， =0.001和 =4.579， =0.001）水平，增加了EF（ =11.264， =0.002和 =10.356， =0.001）和LVFS（ =8.246， =0.002和 =7.824， =0.001），下调了AngⅡ（ =3.126， =0.001和 =2.853， =0.001）、ALD（ =3.854， =0.004和 =3.164， =0.004）、PRA（ =3.126， =0.004和 =3.063， =0.004）、IL -1β（ =2.964， =0.001和 =2.765， =0.001）、IL -6（ =4.865， =0.002和 =4.275， =0.002）和TNF -α（ =3.146， =0.002和 =2.973， =0.002）的表达。另外，它们下调了TGF -β1（ =4.657， =0.001和 =4.176， =0.00 <,sub>1）、p - Smad2/Smad2（ =9.687， =0.001和 =6.753， =0.001）和p - Smad3/Smad3（ =6.477， =0.002和 =,4.754， =0.002）的蛋白水平。结论 茶多酚通过抑制肾素 - 血管紧张素 - 醛固酮系统及TGF -β1/Smads通路的激活对大鼠心力衰竭起到保护作用。
