Objective To explore effects and action mechanism of Fu Fang Ku Shen Zhu She Ye on adverse reactions of 5-fluorouracil(5-FU)chemotherapy in rats with liver cancer.Methods The rat model of liver cancer was constructed by diethylnitrosamine(DEN).Model rats were divided into the liver cancer group,the chemotherapy group and the chemotherapy+Fu Fang-L/M/H groups.At 24 h after modeling,the chemotherapy group and the chemotherapy+Fu Fang groups were given intraperitoneally injection of 5-FU(100 mg/kg,once/week),and the chemotherapy+Fu Fang-L/M/H groups were given intraperitoneally injection of Fu Fang Ku Shen Zhu She Ye[0.7,1.4 and 2.8 mL/kg,once/d]for 8 weeks.The cardiac function,myocardial injury markers and pathological changes of myocardial tissue were compared between different groups.Serum levels of brain natriuretic peptide(BNP),cardiac troponin I(cTnI)and creatine kinase MB(CK-MB)were detected by enzyme-linked immunosorbent assay.The expression levels of glucose-regulating protein 78(GRP78),activating transcription factor 6(ATF6)and endoplasmic reticulum stress-related protein(CHOP)in myocardial tissue were detected by Western blot assay.Changes of immune function indexes were compared between different groups.Results Compared with the liver cancer group,left ventricular ejection fraction(LVEF)and left ventricular anterior wall thickness in systole(LVAWs)were decreased in the chemotherapy group(P＜0.05),left ventricular end diameter in systole(LVEDs),levels of BNP,cTnI and CK-MB were increased(P＜0.05),levels of tumor necrosis factor α(TNF-α),interleukin(IL)-1β and IL-6 in myocardial tissue,expression levels of GRP78,ATF6 and CHOP were increased(P＜0.05).Levels of CD3+,CD4+,CD4+/CD8+,IgG,IgM and IgA were decreased in the chemotherapy group(P＜0.05).The myocardial tissue was disordered,vacuolated and infiltrated by inflammatory cells.Compared with the chemotherapy group,the above indexes and pathological changes of myocardial tissue were significantly improved in the chemotherapy+Fu Fang-L/M/H groups,and the improvement was more significant in the chemotherapy+Fu Fang-H group.Conclusion Fu Fang Ku Shen Zhu She Ye injection can alleviate cardiotoxic injury induced by 5-FU in rats with liver cancer,which may be related to alleviating endoplasmic reticulum stress.It can also alleviate immunosuppression.

Objective To explore effects and action mechanism of Fu Fang Ku Shen Zhu She Ye on adverse reactions of 5-fluorouracil(5-FU)chemotherapy in rats with liver cancer.Methods The rat model of liver cancer was constructed by diethylnitrosamine(DEN).Model rats were divided into the liver cancer group,the chemotherapy group and the chemotherapy+Fu Fang-L/M/H groups.At 24 h after modeling,the chemotherapy group and the chemotherapy+Fu Fang groups were given intraperitoneally injection of 5-FU(100 mg/kg,once/week),and the chemotherapy+Fu Fang-L/M/H groups were given intraperitoneally injection of Fu Fang Ku Shen Zhu She Ye[0.7,1.4 and 2.8 mL/kg,once/d]for 8 weeks.The cardiac function,myocardial injury markers and pathological changes of myocardial tissue were compared between different groups.Serum levels of brain natriuretic peptide(BNP),cardiac troponin I(cTnI)and creatine kinase MB(CK-MB)were detected by enzyme-linked immunosorbent assay.The expression levels of glucose-regulating protein 78(GRP78),activating transcription factor 6(ATF6)and endoplasmic reticulum stress-related protein(CHOP)in myocardial tissue were detected by Western blot assay.Changes of immune function indexes were compared between different groups.Results Compared with the liver cancer group,left ventricular ejection fraction(LVEF)and left ventricular anterior wall thickness in systole(LVAWs)were decreased in the chemotherapy group(P＜0.05),left ventricular end diameter in systole(LVEDs),levels of BNP,cTnI and CK-MB were increased(P＜0.05),levels of tumor necrosis factor α(TNF-α),interleukin(IL)-1β and IL-6 in myocardial tissue,expression levels of GRP78,ATF6 and CHOP were increased(P＜0.05).Levels of CD3+,CD4+,CD4+/CD8+,IgG,IgM and IgA were decreased in the chemotherapy group(P＜0.05).The myocardial tissue was disordered,vacuolated and infiltrated by inflammatory cells.Compared with the chemotherapy group,the above indexes and pathological changes of myocardial tissue were significantly improved in the chemotherapy+Fu Fang-L/M/H groups,and the improvement was more significant in the chemotherapy+Fu Fang-H group.Conclusion Fu Fang Ku Shen Zhu She Ye injection can alleviate cardiotoxic injury induced by 5-FU in rats with liver cancer,which may be related to alleviating endoplasmic reticulum stress.It can also alleviate immunosuppression.

ObjectiveTo investigate the role of lymphocyte apoptosis and endoplasmic reticulum stress (ERS) on the development of sepsis and their association with the prognosis of sepsis patients.Methods A prospective cohort study was conducted. Seventy septic patients admitted to intensive care unit (ICU) of Shanghai East Hospital of Tongji University were enrolled. Blood samples were collected on days 1, 3 and 7 to measure percentage of circulating apoptotic lymphocyte with flow cytometry analysis. The relative expressions of endoplasmic reticulum specific glucose regulated protein 78 (GRP78) mRNA and transcription factor CHOP mRNA were measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). The correlation between CHOP mRNA expression and percentage of circulating apoptotic lymphocyte was analyzed by Spearman relative analysis. The patients were divided into death (n = 23) and survival subgroups (n = 47). Twenty healthy volunteers during the same period were selected as the healthy control group.Results① Rate of lymphocyte apoptosis: compared with healthy control group [(2.86±0.66)%], septic patients, either survival or death subgroup, exhibited higher rate of lymphocyte apoptosis on days 1, 3 and 7 [survival subgroup: (12.44±4.43)%, (8.57±3.38)%, (6.78±3.35)%; death subgroup: (14.42±2.01)%, (11.32±2.53)%, (8.87±3.62)%, allP< 0.01], and it was obvious on day 1, and the phenomenon became less marked gradually. The rate of circulating apoptotic lymphocytes did not differ between the death and survival subgroups on day 1, but there was a significant difference in the rate on day 3 and day 7 (bothP< 0.05).② The expression of CHOP mRNA (2-ΔΔCt):compared with that in healthy controls [(2.56±1.09)×10-3], CHOP mRNA expression was increased on days 1, 3 and 7 in septic patients [survival subgroup: (5.83±1.96)×10-3, (4.24±1.60)×10-3, (4.15±1.64)×10-3, death subgroup:(37.20±20.70)×10-3, (18.80±13.90)×10-3, (9.28±7.78)×10-3, allP< 0.01], and it was more obvious in the death subgroup, as it was increased by 6.38, 4.43, and 2.24 folds (P values was 0.000, 0.000, and 0.001), but it decreased rapidly in death subgroup.③ The expression of GRP78 mRNA (2-ΔΔCt): compared with healthy controls [(3.31±2.04 )×10-3], the expression of GRP78 mRNA in both survival and death subgroups increased in septic patients on day 1 [(5.83±2.00)×10-3, (11.30±6.48)×10-3, bothP< 0.01], and they decreased subsequently. The expression of GRP78 mRNA in the survival subgroup declined to the levels of the healthy control group on day 3 and day 7 [3 days: (3.99±1.60)×10-3, 7 days: (3.30±1.35)×10-3, bothP> 0.05], and GRP78 mRNA expression in the death subgroup was gradually lowered, but it was still higher than that in the healthy control group [3 days: (7.27± 3.64)×10-3, 7 days: (5.23±1.94)×10-3, bothP< 0.01].④ Spearman relative analysis showed that the expression of CHOP mRNA was positively correlated with the rate of lymphocyte apoptosis (r = 0.414,P = 0.000 ).Conclusion The increase in the rate of lymphocyte apoptosis and activation of ERS play an important role in the development of sepsis, and it is associated with worse outcome in the septic patients.

AIM To investigate the effect of resveratrol on human liver cancer HepG2, and to study the function of resveratrol in inducing HepG2 apoptosis. METHODS HepG2 cells were treated with resveratrol at various concentrations. MTT assay was used to examine growth and proliferation of HepG2 cells after treatment with resveratrol for 24 hours. HE staining and electromicroscope were used to observe the morphology of apoptotic cells, and TUNEL, flow cytometry were also used to analyze the HepG2 apoptosis. RESULTS Resveratrol significantly inhibited growth and proliferation of HepG2 cells in dose dependent manner. And resveratrol also induced the apoptosis of HepG2 cells. CONCLUSION Resveratrol may inhibit HepG2 cell growth and proliferation through inducing apoptosis.