Efficacy Evaluation And Mechanism Of Elemene In Improving Postembolization Syndrome In Patients After Transcatheter Arterial Chemoembolization

Objective:To observe the occurrence of symptoms such as fever,nausea and vomiting,and liver pain in hepatocellular carcinoma（HCC）after transcatheter arterial chemoembolization（TACE）,and to study the improvement effect and related mechanisms of elemene on Postembolization syndrome（PES）after TACE.Methods:This study was divided into two parts:clinical efficacy evaluation and in vitro experiment.The first part is the clinical efficacy evaluation:（1）This study used a retrospective analysis to include 107 patients with HCC who were admitted to the Department of Hepatobiliary Surgery,Affiliated Hospital of Southwest Medical University from May 2017 to May2020 and met the inclusion criteria.Divided into two groups A and B.Group A used elemene after TACE and group B did not use elemene after TACE.Among them,67 patients from October 2018 to May 2020 were divided into group A Group（Elemene has been used in the Department of Hepatobiliary Surgery during this period）;40 patients were admitted from May 2017 to October 2018and were divided into group B（elemene was not used in the Department of Hepatobiliary Surgery during this period）.（2）Recorded the gender,age and other Baseline characteristics of each group of patients.（3）Recorded the incidence of fever after TACE in each group.（4）Recorded the incidence of nausea and vomiting after TACE in each group.（5）Recorded the incidence of liver pain in each group.（6）Recorded the incidence of Myelosuppression after TACE in each group.（7）Recorded the hospital stay after TACE in each group.The second part was in vitro experiment:（1）HL-7702 cells were cultured in vitro,and Cocl₂ induced cells were used to establish a hypoxic injury model.A blank control group（group A）,β-elemene group（group B）,Cocl₂ group（group C）andβ-Elemene+Cocl₂ group（group D）.（2）CCK-8 method was used to detect the cell viability of each group.（3）the content of malondialdehyde（MDA）,lactate dehydrogenase（LDH）and superoxide dismutase（SOD）of each group was detected by the kit.（4）each group was detected by DCFH-DA staining Cell reactive oxygen species（ROS）content.（5）Hoechst staining method to detect cell apoptosis in each group.（6）Western blotting was used to detect the expression levels of TLR4 and NF-κB P65 protein in each group.Results:The results of clinical efficacy evaluation showed:（1）Patient baseline characteristics were similar between both groups.（2）Fever occurred in 10 patients in the elemene group,with an incidence rate of 14.93%,and 13patients in the non-elemene group developed fever after TACE,with an incidence rate of 32.50%.The P value between the two groups were 0.032.The incidence of fever in the elemene group was lower than that in the non-elemene group,and the difference was statistically significant.（3）10 patients in the elemene group developed nausea and vomiting after TACE,the incidence rate was 14.93%,and 14 patients in the non-elemene group developed nausea and vomiting after TACE,the incidence rate was 35.00%.The P value between the both groups were 0.016.The incidence of nausea and vomiting in the elemene group was lower than that in the non-elemene group,and the difference was statistically significant.（4）Twenty-six patients in the elemene group experienced liver pain after TACE,an incidence rate of 38.81%,and 27 patients in the non-elemene group experienced liver pain after TACE,an incidence rate of 67.50%.The P value between the both groups were 0.004.The incidence of liver pain in the elemene group was lower than that in the non-elemene group,and the difference was statistically significant.（5）Three patients in the elemene group developed Myelosuppression after TACE,the incidence was 4.48%,and 8 patients in the non-elemene group developed Myelosuppression after TACE,the incidence was 20.00%.The P value between the both groups were 0.026.The incidence of Myelosuppression in the elemene group was lower than that of the non-elemene group,and the difference was statistically significant.（6）The hospital stay after TACE in the elemene group was 4.25±2.22（day）,and the hospital stay after TACE in the non-elemene group was 7.55±5.90（day）.The comparison between the both groups were P<0.01,the difference was statistically significant.The results of in vitro experiments showed:（1）When the concentration ofβ-elemene≥20μg/m L,it significantly inhibits HL-7702 cells（P<0.05）.（2）compared with the blank control group,when the concentration of Cocl₂ is 300μmol/L and above,it can significantly reduce the viability of HL-7702 cells（P<0.05）,the concentration of Cocl₂ 300μmol/L was set as the hypoxia modeling concentration in subsequent experiments.（3）the Cocl₂ group compared with the blank control group,the cell viability of the Cocl₂ group was significantly reduced（P<0.05）,theβ-elemene+Cocl₂ group was compared with the Cocl₂ group,cell viability was improved（P<0.05）.（4）the content of MDA and LDH in the Cocl₂ group was higher than that in the blank control group,and the content of SOD was lower than that in the blank control group（P<0.05）.In theβ-elemene+Cocl₂ group,MDA,The content of LDH was lower than that of the Cocl₂ group,and the content of SOD was higher than that of the Cocl₂group（P<0.05）.（5）the content of active oxygen in theβ-elemene+Cocl₂ group was lower than that of the Cocl₂ group（P<0.05）.（6）theβ-elemene+Cocl₂group’s cell apoptosis rate was lower than that in the Cocl₂ group（P<0.05）.（7）the cell morphological damage in theβ-elemene+Cocl2 group was lower than that in the Cocl2 group.（8）the expression level of TLR4/NF-κB P65 inflammatory pathway protein in theβ-elemene+Cocl₂ group was lower than that in the Cocl₂ group（P<0.05）.Conclusion:For patients with HCC,the use of elemene after TACE can effectively reduce the incidence of PES,reduce the incidence of Myelosuppression,and shorten the patient’s hospital stay.The mechanism may be related to inhibiting the activation of TLR4/NF-κB inflammatory signaling pathway and reducing oxidative stress.