Shenfu injection prevents sepsis-induced myocardial injury by inhibiting mitochondrial apoptosis

• Published in: Journal of ethnopharmacology 2020-10, Vol.261, p.113068-113068, Article 113068
• Main Authors: Xu, Po, Zhang, Wen-Qing, Xie, Jing, Wen, Ying-Shi, Zhang, Guo-Xing, Lu, Shi-Qi
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Heart Diseases - etiology; Heart Diseases - metabolism; Heart Diseases - pathology; Heart Diseases - prevention & control; Male; Mice, Inbred C57BL; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondria, Heart - ultrastructure; Mitochondrial apoptosis; Myocardial injury; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Sepsis; Sepsis - complications; Sepsis - drug therapy; Shenfu injection (SFI); Signal Transduction
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.113068

Shenfu injection (SFI) is a well-known Chinese herbal medicine widely used in the treatment of septic shock in China. The aims of this study are to investigate the protective effects of SFI on sepsis-induced myocardial injury in mice and to identify the underlying mechanism of action. Seventy-two male C57/B6J mice (5–6 weeks old) were randomly divided into five groups: control (NC), sham sepsis (sham), sepsis (Lipopolysaccharide- LPS), sepsis treated with a low dose SFI, and sepsis treated with a high dose SFI. Sepsis was induced in mice by intraperitoneal injection of LPS. Myocardial tissue samples were collected from different groups at 6 h, 12 h, and 24 h post-LPS injection. Myocardial injury was examined using hematoxylin-eosin (H&E) and TUNEL staining. Western-blot analysis was performed to determine the protein expression of B-cell lymphoma 2 (Bcl-2), BH3 interacting-domain death agonist (Bid), truncated-Bid (t-Bid) and caspase-9 in all the groups. Moreover, the structural changes in the mitochondria of cardiomyocytes were also observed by transmission electron microscopy. H&E staining revealed structural damage, local necrosis, interstitial edema, inflammatory cell infiltration and vacuolar changes in the myocardial tissue in the sepsis (LPS) group; almost intact myocardial tissue was observed in the high dose SFI group with improvements in interstitial edema and inflammatory cell infiltration. We observed that LPS-induced cardiomyocyte apoptosis was significantly improved with high dose SFI as compared with sepsis (LPS) group (P ˂ 0.05). LPS was found to decrease the protein expression of Bcl-2 and increase the level of Bid, t-Bid and caspase-9. Treatment with SFI significantly increased the Bcl-2 protein expression (P ˂ 0.05) and decreased the protein expression of Bid, t-Bid and caspase-9 as compared with LPS group (P ˂ 0.05). Markedly swollen myocardial mitochondria with partial vacuolation were observed in LPS treated mice while SFI treatment was found to significantly improve the LPS-induced morphological damage of the mitochondria. In conclusion, we demonstrate that SFI protects against sepsis-induced myocardial injury in mice through the suppression of myocardial apoptosis. It upregulates the protein expression of Bcl-2 and downregulates the protein expression of Bid, t-Bid and caspase-9, and alleviates sepsis-induced mitochondrial damage. [Display omitted]