摘要
目的基于抑制转化生长因子-β_(1)(TGF-β_(1))/Smad3通路探讨芍药苷对急性心肌梗死后心室重塑的影响。方法将40只SD大鼠随机分为假手术组、模型组、曲美他嗪组和芍药苷高、低剂量组,每组8只。除假手术组外,其余各组通过结扎大鼠冠状动脉左前降支建立急性心肌梗死大鼠模型。曲美他嗪组大鼠灌胃10mg/(kg·d)曲美他嗪,芍药苷高、低剂量组大鼠灌胃10 mg/(kg·d)和5 mg/(kg·d)芍药苷,假手术组和模型组灌胃生理盐水,均连续4周。超声心电图评估大鼠心功能,ELISA试剂盒检测大鼠血清中白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,TTC染色检测大鼠心肌梗死面积,HE染色观察大鼠心肌结构变化,Masson染色观察大鼠心肌胶原沉积情况,Western blot法检测大鼠心肌Ⅰ型胶原、Ⅲ型胶原、TGF-β_(1)、p-Smad3和Smad3表达情况。结果与假手术组比较,模型组大鼠射血分数(EF)、左室短轴缩短分数(FS)均显著降低(P均<0.05),左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)和血清TNF-α、IL-6水平均显著升高(P均<0.05);大鼠心肌排列紊乱,有明显炎性细胞浸润和间质水肿,胶原沉积面积和心肌组织中Ⅰ型胶原、Ⅲ型胶原、TGF-β_(1)、p-Smad3表达水平均显著增高(P均<0.05)。与模型组比较,曲美他嗪组、芍药苷低剂量组和芍药苷高剂量组大鼠EF和FS均显著升高(P均<0.05),LVIDs、LVIDd,血清TNF-α、IL-6水平,心肌梗死面积、胶原沉积面积,心肌组织中Ⅰ型胶原、Ⅲ型胶原、TGF-β_(1)、p-Smad3表达量均显著降低(P均<0.05),且芍药苷高剂量组改善情况均优于芍药苷低剂量组(P均<0.05)。结论芍药苷可通过抑制TGF-β_(1)/Smad3通路改善急性心肌梗死后心室重塑。
Objective It is to explore the effect of paeoniflorin on ventricular remodeling after acute myocardial infarction by inhibiting the transforming growth factor-β_(1)(TGF-β_(1))/Smad3 pathway.Methods Forty SD rats were randomly divided into sham operation group,model group,trimetazidine group and paeoniflorin high-dose and low-dose groups,with 8 rats in each group.Except for the sham-operated group,the left anterior descending coronary artery of the rats in the other groups was ligated to establish models of acute myocardial infarction.The rats in the trimetazidine group were given 10 mg/(kg·d)trimetazidine by gavage,the rats in the high-dose and low-dose paeoniflorin groups were respectively given 10 mg/(kg·d)and 5 mg/(kg·d)paeoniflorin by gavage,the rats in the sham operation group and the model group were given normal saline by gavage,all the groups were treated for 4 weeks.The cardiac function of the rats was evaluated by echocardiography,the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the serum of the rats were detected by ELISA kit,the myocardial infarction area of the rats was detected by TTC staining,the myocardial structure changes of the rats were observed by HE staining,the collagen deposition in rat myocardial cells was observed by Masson staining,and the expressions of typeⅠcollagen,typeⅢcollagen,TGF-β_(1),p-Smad3 and Smad3 were detected by Western blot.Results Compared with the sham-operated group,the ejection fraction(EF)and left ventricular short-axis fractional shortening(FS)in the model group were significantly decreased(all P<0.05),and the left ventricular end-diastolic inner diameter(LVIDd)and left ventricular end-systolic inner diameter(LVIDs)and serum levels of TNF-αand IL-6 were significantly increased(all P<0.05);myocardial arrangement in the rats was disordered,with obvious inflammatory cell infiltration and interstitial edema,collagen deposition area and the expression levels of typeⅠcollagen,typeⅢcollagen,TGF-β_(1) and p-Smad3 in myocardial tissue w
作者
闫娜
杨妮
董晗
魏平
YAN Na;YANG Ni;DONG Han;WEI Ping(Affiliated Hospital of Yan’an University, Yan’an 716000, Shaanxi, China;The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi, China;School of Basic Medicine, Xi’an Jiaotong University, Xi’an 710049, Shaanxi, China)
出处
《现代中西医结合杂志》
CAS
2022年第5期624-629,共6页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
陕西省重点研发计划项目(2019SF-1411)。
