| ObjectiveTo investigate the influence and mechanism of Tongxinluo capsule on the rats of myocardial fibrosis induced by isoproterenol (ISO).Based on the TGF-β1/TAK1 signaling pathways, observed TGF-β1、TAK1 concentration changes in rat serum and myocardial tissue,Further to find the laboratory basis of Tongxinluo capsule to prevent and reverse myocardial fibrosis, slow cardiac remodeling and improve the heart function.MethodsThe rats were randomly assigned into five groups (n=10 per group) that included: Blank group,model group,Captopril group,high dose group of Tongxinluo capsule low dose group of Tong xinluo capsule.The blank group was injected intradermally with sterile saline on the back of the animals, while the other groups were injected with ISO 5mg/(kg·d) for seven days. The blank group and model group rats were administered with distilled water through intro-gastric for 21 days. The captopril group was administered with Captopril by gavage for 21 days. Tongxinluo capsule groups were administered with Tongxinluo capsule in different dosages by gavage daily for 21 days. Then used Masson and HE staining methods to observe the myocardial morphology measured Myocardial collagen volume fraction, heart weight and heart index.used E1ISA to detecte expression of TGF-β1 and TAK1 in serum and myocardial tissue.Statistical processing by SPSS 21.0.Results1. HE and Masson staining:The myocardial tissue of rats in Captopril group and Tongxinluo capsule groups was improved in different degree.Such as the degree of myocardial cell degeneration, necrosis,myocardial fibrosis inflammatory cell, infiltr-ation and fibrous tissue proliferation.The Tongxinluo capsule high dose group had a preponderant role.2. Myocardial tissue collagen volume fraction (CVF):Compared with the blank group,the CVF of model group was increased significantly (P<0.01);Compared with model group,the CVF of Drug intervention groups were decreased significantly (P<0.05);Compareed with Tongxinluo low dose group,the CVF of Tongxinluo high dose group was reduced significantly (P<0.01).3. The heart weight and the heart weight index (HWI):Compared with the blank group,the heart weight and heart weight index of model group was increased significantly (P<0.05); Compared with the model group,the heart weight and heart weight index of Drug intervention groups were decreased significantly(.P<0.05);The heart weight and HWI of Tongxinluo capsule high dose group was the lowest (P<0.05).4. The expression of TGF-β1 and TAK1 in the cardiac muscle tissue and serum of rats:Compared with the model group, the expression of TGF-β1 and TAK1 were decreased in drug intervention groups significantly(P<0.01).Compared with the captopril group,the expression of TGF-β1 and TAK1 were higher in the Tongxinluo capsule groups(.P<0.01),and the expression of TGF-β1 and TAK1 was lower in Tongxinluo capsule high dose group compared with the Tongxinluo capsule low dose group(P<0.01).5. The correlation analysis of TGF-β1 and TAK1 in the cardiac muscle tissue and serum of rats:This study found that in the blank group, the expression of TGF-β1 and TAK1 was lowest in thecardiac muscle tissue and serum;the expression of TGF-β1 and TAK1 was highest in the the model group,both was a positive correlation (P<0.01);The expression of TGF-β1 and TAK1 were positively correlated in the Drug intervention group, and relevant relations (P<0.05).ConclusionThe size and weight of heart were increased after injection of ISO 5mg/(kg·d) for seven days, and the ventricular dilatation was appeared. The Masson staining showed that the myocardial cells were swelling obviously, degenerated and necrotic, the myocardial fiber was fractured and disorganized, the cell nucleus were enlarged, fibrous tissue was hyperplastic, and the expression of TGF-β1 and TAK1 were increased obviously.The Tongxinluo capsule can reverse the myocardial fibrosis of rats induced by ISO, reduce the height of heart and CVF, and decrease the expression of TGF-β1 and TAK1 in the serum and myocardial tissue. The mechanism may related with the function on the TGF-β1/TAK1 signaling pathways.May be related to its role in the TGF-β1/TAK1 signaling pathways, play a role of anti myocardial fibrosis, and Tongxinluo capsule on myocardial protection are dose dependent. |
