[Toxic effects of combination of Aconiti Lateralis Radix Praeparata with Trichosanthis Fructus on inflammatory response and myocardial fibrosis in pressure overload rats based on β2-AR/PKA signal].

: 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.