ABSTRACT
Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.
Subject(s)
Animals , Female , Humans , Male , Rats , C-Reactive Protein , Genetics , Allergy and Immunology , Cecum , General Surgery , Drugs, Chinese Herbal , Chemistry , Heart , Interleukin-6 , Genetics , Allergy and Immunology , Ligation , Myocardium , Allergy and Immunology , Phenanthrenes , Chemistry , Punctures , Salvia miltiorrhiza , Chemistry , Sepsis , Drug Therapy , Allergy and Immunology , Troponin T , Genetics , Allergy and Immunology , Tumor Necrosis Factor-alpha , Genetics , Allergy and ImmunologyABSTRACT
Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.
Subject(s)
Animals , Female , Humans , Male , Rats , C-Reactive Protein , Genetics , Allergy and Immunology , Cecum , General Surgery , Drugs, Chinese Herbal , Chemistry , Heart , Interleukin-6 , Genetics , Allergy and Immunology , Ligation , Myocardium , Allergy and Immunology , Phenanthrenes , Chemistry , Punctures , Salvia miltiorrhiza , Chemistry , Sepsis , Drug Therapy , Allergy and Immunology , Troponin T , Genetics , Allergy and Immunology , Tumor Necrosis Factor-alpha , Genetics , Allergy and ImmunologyABSTRACT
Objective To study the changes of S100βin serum and brain tissue of rats with sepsisassociated encephalopathy (SAE).Methods After placement of pole plates of electroencephalogram (EEG) on the brain cortex,thirty SD rats were randomly (random number) divided into three groups post hoc:sepsis group in which rats were made to be sepsis models by cecal ligation and puncture (n =18),normal group (n =6) and sham operation group (n =6).The sepsis-associated encephalopathy was diagnosed with electroencephalogram taken by RM6240 physiological signal recorder.Meanwhile,heart rate and blood pressure were recorded.Eight hours later,serum and brain tissue of sacrificed rats were taken for measuring S100β.The results ware analyzed with one-way ANOVA.Results Of 18 sepsis rats,3 were dead,8 without SAE and 7 with SAE.The levels of S100βin serum and brain tissue of rats with SAE group were significantly higher than those in normal group and sham operation proup (P ＜ 0.05).The Ratio of brain/serum S100βin rats with SAE group was higher than that in rats without SAE (1.74 vs 1.51,P ＜ 0.05).Conclusions Significantly high level of serum S100βwas a reliable bio-marker for diagnosis of SAE in rats.