| Objective:1.Investigate the effects of different chemotherapy regiments on cognitive function of breast cancer patients through clinical neuropsychological tests;2.Morris water maze test was used to explore the effects of different chemotherapy drugs on the cognitive function of C57BL/6 mice;3.The relationship between cognitive function and intestinal flora abundance and diversity of C57BL/6 mice after chemotherapy was studied by 16 S r RNA high-throughput sequencing.Methods:1.FACT-Cog and Mo CA were respectively used to test subjective and objective cognitive abilities of breast cancer patients who were admitted to the Department of Breast,The First Hospital of Shanxi Medical University from October 2019 to October2021,7 days before chemotherapy(T1),4 weeks after chemotherapy(T2),and 6 months after T2(T3).2.Twenty C57BL/6 mice were randomly divided into epirubicin group(group E),paclitaxel group(group P),cyclophosphamide group(group C)and control group(group S),and 5 mice in each group were intrabitoneally injected with epirubicin(4mg/kg),paclitaxel(20 mg/kg),cyclophosphamide(50mg/kg)and 0.9% Na Cl solution.Morris water maze test was performed 4 cycles after administration,and feces of mice were collected for 16 S r RNA high-throughput sequencing to detect intestinal flora.Results:1.A retrospective study of 364 patients with breast cancer(mean age 53 years;Of these,52% were treated with anthracycline-containing chemotherapy)and 372 controls(mean age 53 years)were assessed.(1)compared with the control group,from T1 to T3,the chemotherapy group had FACT-Cog total score(P=0.039)and four subscales(P=0.014;0.025;0.033;0.023)significantly increased cognitive difficulties.In the chemotherapy group,chemotherapy with anthracycline was significantly associated with a lower FACT-Cog total score from T1 to T2(P=0.044).(2)compared with the control group,from T1 to T3,cognitive difficulties on the Mo CA total score(P=0.031)were significantly increased in the chemotherapy group.In the chemotherapy group,chemotherapy with anthracycline was significantly associated with lower total Mo CA scores from T1 to T3(P=0.039).2.Morris water maze test:(1)compared with the control group,the escape incubation period of group E was significantly longer during 5 days of training(p=0.032;0.025;0.014;0.028;0.036),indicating that the group E had impaired learning ability.(2)compared with the control group,the time spent in the target quadrant of the group E was significantly reduced(P =0.018),indicating that the spatial memory ability of the group E was impaired.3.16 sr DNA sequencing results:(1)Alpha diversity analysis: there were no significant changes in Chao,Ace,Simpson and Shannon indexes among the four groups(P=0.7877,0.7877,0.6843,0.3987),indicating that the intestinal flora richness and diversity of the four groups were similar.(2)Beta diversity analysis: compared with the control group,the data of the epirubicin group were different in both density and spatial distance,indicating that the intestinal microflora structure of mice in the epirubicin group was changed.(3)compared with the control group,the relative abundance of Lachnospiraceae＿NK4B4＿group in epirubicin group was significantly decreased(P=0.02536986).Conclusion:1.Chemotherapy can lead to cognitive impairment in breast cancer patients,and these effects are long-term irreversible,especially the effect of anthracycline.In addition to the objective assessment of patients’ cognitive function,the assessment of patients’ subjective cognitive function is also an important aspect of CRCI.2.The spatial learning and memory ability of mice injected with epirubicin was decreased,and the structure of intestinal microflora was changed.The relative abundance of Lachnospiraceae＿NK4B4＿group bacteria was significantly decreased,and the correlation between the two bacteria suggested that epirubicin might affect cognitive function by changing the intestinal microflora of mice. |
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