Mechanism on the protective effect of coptisine against myocardial injury in sepsis mice

Zhou You; Han Xiaoman; Lei Yiming; Li Jing; Du Jiamin; Wei Jie; Zhou Chenliang

doi:10.3969/j.issn.1002-1949.2025.04.009

Abstract：Objective To explore the effects and mechanisms of coptisine(COP)on myocardial injury induced by sepsis in mice.Methods Sixty male C57BL/6 mice were randomly divided into three groups:Sham group,sepsis group(CLP group)and treatment group(CLP+COP group)with 20 mice in each group.In the CLP and CLP+COP groups,sepsis was induced by cecal ligation and puncture(CLP)surgery,while the Sham group underwent the same surgical procedure without CLP.Mice in the CLP+COP group were administered COP by daily gavage from 3 days prior to surgery until 4 days after surgery.The survival rate of the three groups was recorded daily for one week after surgery.After 7×24 h postoperatively,cardiac function was assessed by echocardiography.Blood samples were collected to measure the levels of interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α((TNF-α),lactate dehydrogenase(LDH),creatine kinase-MB isoenzyme(CK-MB),and cardiac troponin I(cTnI)in serum.Subsequently,heart tissues from each group were collected for HE staining,reactive oxygen species(ROS)staining and transmission electron microscopy(TEM)analysis.Finally,Western blot was performed to examine the expression of apoptosis-related proteins(Bax,Bcl-2)and oxidative stress-related pathway proteins(Nrf2,HO-1)in myocardial tissues.Results Compared with the Sham group,the CLP group mice exhibited the significant decrease in survival rate,severe cardiac dysfunction,disorganized and sparse myocardial cell arrangement,a significant increase in myocardial injury markers and inflammatory factors,damaged mitochondrial structure,and a marked increase in ROS levels in the tissues(all P<0.05).Compared with CLP group,the survival rate in CLP+COP group increased,but there was no significant difference(P>0.05).COP effectively improved cardiac function and myocardial pathological changes,reduced myocardial injury markers and inflammatory factors,alleviated mitochondrial damage and decreased oxidative stress.Western blot results showed that the expression level of Bax in the myocardial tissue of the CLP group was significantly higher than that in the Sham group,while the expression levels of Bcl-2,Nrf2 and HO-1 were significantly lower(all P<0.05).Compared with the CLP group,the CLP+COP group mice showed a reduced Bax expression level and significantly increased expression levels of Bcl-2,Nrf2 and HO-1(all P<0.05).Conclusions COP can alleviate myocardial injury in sepsis mice,and its mechanism may be closely related to the activation of the Nrf2/HO-1 pathway,the reduction of mitochondrial oxidative stress and the inhibition of apoptosis.