RESUMO
To study the effects of combination of Aconiti Lateralis Radix Praeparata( Fuzi) with Trichosanthis Fructus( Gualou) on cardiac function,electrocardiogram,inflammatory response and myocardial fibrosis in pressure overload( PO) rats,and further explore the mechanism based on β2-AR/PKA signaling. PO rat model was established by constricting the abdominal aorta. Twelve weeks after the operation,these rats were randomly divided into model goup( PO),low dose Fuzi group( FL,5. 4 g·kg-1·d-1),Gualou group( GL,5. 4 g·kg-1·d-1),Fuzi and Gualou combination group( FG,5. 4 g·kg-1·d-1+5. 4 g·kg-1·d-1) and high dose Fuzi group( FH,10. 8 g·kg-1·d-1). At the same time,sham operation group was set. After intervention for 6 weeks,carotid blood pressure,cardiac function,electrocardiogram and heart mass index were measured. HE staining was used to observe the inflammatory response in the rat heart and kidney. Masson staining was used to determine the myocardial fibrosis. Western blot was used to detect the protein expression of β2-AR and PKA. As compared with sham operation group,the blood pressure and heart mass index were obviously increased in PO model group,but there was no significant difference in various treatment groups in the above indexes. As compared with PO model group,FH treatment significantly increased the ejection fraction( EF) and GL treatment effectively enhanced the cardiac output( CO),but other treatment groups had no significant effect on these parameters. Moreover,FG treatment can synergistically attenuate QT and QTc internal prolongation,but it also aggravated inflammatory response in the heart and kidney tissues and promoted myocardial fibrosis as compared to FZ or GL alone treatment,with toxic effects equivalent to FH treatment group. Following FG and FH treatment,simultaneously,β2-AR and PKA protein levels were significantly elevated,indicating that the increasing toxicity of FG could be associated with activation of β2-AR/PKA signaling. These results suggested that combination of FZ and GL could synergistically enhance toxicity of FZ in special pathological states such as pressure overload,and caution should be taken in clinical application.
Assuntos
Animais , Ratos , Aconitum , Medicamentos de Ervas Chinesas , Fibrose , Frutas , Transdução de SinaisRESUMO
Objective: To investigate the features of cardiotoxicity and neurotoxicity and the influence on vascular endothelial of ethanol extract of Aconiti Radix (AR). Methods: Totally 45 Wistar rats were randomly divided into four groups, and ig given low-, middle-, and high-dose 70% ethanol extract of AR (in the raw drug dose of 2.5, 5.0, and 7.5 g/kg respectively) for 15 d. The toxic reaction and death condition were observed during administration. The electrocardiogram (ECG) change was tested after administration. Blood was collected for blood routine and blood biochemistry analysis. Brain was harvested for calculating viscera index and pathological examination. Left ventricular and hippocampus were extracted and stained with electron microscope (EM) methods. Results: At the end of treatment, all rats were sacrificed in the high-dose AR group. The mortality and hematologic parameters including RBC, HGB, HCT, ALT, UREA, and GLU were significantly increased in the middle-dose AR groups compared with control group. Arrhythmia especially ventricular arrhythmia occurred in low- and middle-dose AR group. Brain index and number of pyknotic neurons in focal area of hippocampus were significantly increased in middle-dose AR group. EM examination indicated that dissolution of neuronal inclusions, nuclear fragmentation, and coagulation necrosis of glial cells were prominent in the hippocampus tissue in middle-dose AR group. In the middle-dose AR group, the vascular endothelial cells injury and apoptosis were obviously observed in left ventricular and hippocampus separately. Conclusion: The ethanol extract of AR can lead to cardiotoxicity and neurotoxicity especially vascular endothelial injury in dose-dependent manner.
RESUMO
Objective: Shengmai Recipe (SMR) is a Chinese patent medicine used for the treatment of chronic heart disease. In order to further assess the renal-protective effect against ischemia lesion of SMR, the cardioprotective effect of SMR on pressure overload-induced left ventricular (LV) systolic dysfunction and the potential mechanism on alleviating myocardial damage, myocardial fibrosis, and renal ischemia lesion in chronic heart failure (CHF) rats were investigated. Methods: Rats with partially ligated abdominal aorta were randomly divided into model, Sham, and SMR groups. One week after recovery from surgery, animals were preventively ig administered with SMR at the dose of 810 mg/kg once daily for 8 weeks. Cardiac function and structure, endogenous biomarkers (CK-MB and LDH), myocardial fibrosis, and organ pathological change were estimated by echocardiography, immunodepression and velocity method, hematoxylineosin staining, and masson's trichrome staining, respectively. Results: The administration of SMR significantly decreased serum CK-MB and LDH levels and reduced myocardial fibrosis. Interestingly, SMR not only improved cardiac function but also ameliorated kidney injury induced by ischemia in CHF rats. Conclusion: SMR could enhance the LV contractile function, reduce myocardial necrosis, and reverse LV remodeling in CHF rats, and most importantly, SMR could be used to treat the renal ischemia injury in pressure overload rats.