ABSTRACT
Aim To investigate the mechanism of action of Shen-Fu decoction in the prevention and treatment of cardiogenic shock based on network pharmacology and animal experiments. Methods The relevant targets and signaling pathways of cardiogenic shock of Shen-Fu decoction were predicted by network pharmacology, and a cardiogenic shock rat model was created by coronary artery ligation. Before modeling, rats were given the appropriate dose of Shen-Fu decoction or saline by gavage for 14 days according to the group, and real-time mean arterial pressure (MAP) changes were recorded after successful modeling. HE method was used to detect the myocardial histopathological changes of cardiogenic shock. TUNEL method was employed to detect rat myocardial cell apoptosis, and Western blotting was applied to determine the expression levels of rat myocardial Bax, Bcl-2, caspase-3, cleaved caspase-3 proteins. Results A total of 51 potential active ingredients of Shen-Fu decoction were screened out by network pharmacology, 80 targets of co-action with cardiogenic shock, and 43 core targets of close relationship between proteins, and GO enrichment analysis revealed that the core proteins were involved in the biology process (BP), mainly involving positive regulation of apoptotic process. KEGG enrichment analysis showed signaling pathways involving atherosclerosis-related, apoptosis and other signaling pathways. The results of animal model validation showed that Shen-Fu decoction could increase the shock blood pressure of rats with cardiogenic shock and alleviate the pathological changes of myocardial tissue, reduce the degree of apoptosis of rat cardiomyocytes, reduce the expression level of caspase-3, cleaved caspase-3 and Bax protein in rat myocardial tissue, and improve the expression level of Bcl-2 protein in myocardial tissue of rats. Conclusions The potential active ingredient of Shen-Fu decoction may play a role in the prevention and control of cardiogenic shock rats by acting on the target Bax, Bcl-2 to regulate the apoptosis signaling pathway of cardiomyocytes.
ABSTRACT
Objective:To observe the effects of exercise preconditioning on blood-brain barrier (BBB) permeability, and connexin 43 (Cx43) and pannexin 1 (Panx1) protein after cerebral ischemia-reperfusion injury in rats. Methods:Fifty-four male Sprague-Dawley rats were randomly divided into sham group (n = 18), model group (n = 18) and exercise preconditioning group (n = 18). The exercise preconditioning group was trained with treadmill for three weeks before modeling. The middle cerebral arteries were occluded in the model group and the exercise preconditioning group using the modified Koizumi suture. After reperfusion of 24 hours, the rats were assessed with modified Neurological Severity Score (mNSS). The permeability of BBB was observed with Evans blue (EB). The expression of Cx43 and Panx1 was detected with Western blotting and immunohistochemistry in the ischemic tissues. Results:Compared with the model group, the mNSS score decreased in the exercise preconditioning group (P < 0.05), while the Evans blue content and the expression of Cx43 and Panx1 decreased (P < 0.05), as well as the the positive areas of Cx43 and Panx1 (P < 0.05). Conclusion:Exercise preconditioning can improve the permeability of BBB in cerebral ischemia-reperfusion rats, which may associate with down-regulation of Cx43 and Panx1, to protect brain from injury.