| As China's cancer mortality survey reports,the mortality rate of lung cancer patients in China has increased significantly in recent decades,and it has become the highest fatality rate cancer in China.The immune state of the human body is closely related to the tumor and it is the basis and prerequisite for the development of the tumor.The ninety-five percent of the energy required for cell life activity comes from mitochondria,which plays an indispensable role in the maintenance of normal function of immune cells in the body.At present,the relationship between the occurrence and development of lung cancer and immune cell mitochondrial function has not been reported systematically.We proposed the hypothesis that the decrease of mitochondrial function in peripheral blood immune cells is closely related to the occurrence and development of tumors.This article mainly observed the relationship between peripheral blood immune function and mitochondrial ROS,membrane potential and ATP.The research contents mainly include the following three aspects:(1)The changes of immune cell mitochondrial function in peripheral blood of lung cancer patients and normal population;(2)BaP-induced lung cancer model in male Kunming mice;(3)The changes of mitochondrial function in mouse peripheral blood mononuclear cells during the development of BaP-induced lung cancer.This article mainly obtained the following experimental results:(1)Changes in mitochondrial function of peripheral blood mononuclear cells in lung cancer patients and normal people:In the clinical investigation and study of lung cancer patients and normal population,the ROS content of mitochondria in the peripheral blood mononuclear cells in the normal control group was 38.16±9.92,and48.01±8.71 in the lung cancer group,which was significantly higher than that in the normal control group(P<0.01).In the normal control group,the mitochondrial membrane potential of peripheral blood mononuclear cells was 2379.98±641.46,and that of the lung cancer group was 1310.64±210.24.Compared with the normal control group,the mitochondrial membrane potential of the lung cancer group was decreased(P<0.01).The ATP content of peripheral blood mononuclear cells in lung cancer group was 9.30±3.98,which was significantly lower than that in normal control group(14.46±5.02).Thedifferencewasstatisticallysignificant(P<0.01).Subsequently,the mitochondrial membrane potentials of T and B lymphocytes in peripheral blood mononuclear cells were detected by flow cytometry.The mitochondrial membrane potential of CD3~+CD19~-T cells in the control group was 1470.37±219.33,and that of the lung cancer group was 1016.73±238.17.Compared with the normal control group,the mitochondrial membrane potential was significantly decreased in the lung cancer group(P<0.01).The CD3~-CD19~+B in the normal control group was2781.42±648.69 and 953.28±301.50 in the lung cancer group.Compared with the normal control group,the mitochondrial membrane potential was significantly decreased(P<0.01),indicating that the T and B lymphocyte mitochondria function in lung cancer patients were significantly reduced.Further analysis revealed that there were significant changes in mitochondrial ROS,mitochondrial membrane potential,and ATP content in peripheral blood mononuclear cells in patients with various ages.From the above results,compared with the normal control group,the mitochondrial ROS content of peripheral blood mononuclear cells in lung cancer patients was significantly increased,and the mitochondrial membrane potential and ATP synthesis were reduced.It showed that there was obvious oxidative stress in peripheral blood mononuclear cells of patients with lung cancer,and the mitochondrial function was decreased.(2)The establishment of BaP-induced mouse lung cancer model:After 6 weeks of the last administration,the number of tumors in the BaP group(0.13±0.33)and the incidence of lung cancer(10.0%)were not statistically different from those in the control group(0.10±0.31)and the incidence of lung cancer(8.0%)(P>0.05).The number of tumors in the BaP group(0.72±1.01)and lung cancer incidence(46.0%)increased compared with the control group(0.26±0.64)and lung cancer incidence(12.0%)14weeks after the last intragastric administration(P<0.05).At the same time,the number of tumors and the incidence of lung cancer in BaP mice were significantly increased after 14 weeks of the last administration compared with 6 weeks after the last administration(P<0.05).The above results showed that BaP can induce the development of lung cancer in mice.With the prolongation of BaP induction time,the incidence of lung cancer and the number of tumors in the experimental group continue to increase.(3)The changes of mitochondrial function in peripheral blood mononuclear cells of mice during the development of lung cancer caused by BaP:By detecting mitochondrial function of peripheral blood mononuclear cells before and after the occurrence of BaP-induced lung cancer in mice,we found that 6 weeks after the last administration mitochondrial ROS fluorescence values of peripheral blood mononuclear cells was145.67±32.74 in control group,and 186.10±57.23 in BaP group,higher than the control group.The difference was statistically significant(P<0.05).In the control group,the mitochondrial membrane potential of peripheral blood mononuclear cells was 1492.72±348.10,and that of BaP was1250.81±457.75,which was lower than that of the control group.The difference was statistically significant(P<0.05).The ATP value of peripheral blood mononuclear cells was 13.46±3.55 in the control group and10.11±3.50 in the BaP group,which was significantly lower than that of the control group.The difference was statistically significant(P<0.01).Further group detection of T and B lymphocytes in mononuclear cells revealed that the mitochondrial membrane potential of CD3~+CD19~-T cells in the control group was 423.372±103.82,and that in the BaP group was 336.65±87.57,which was significantly lower than that of the control group(P<0.01).The mitochondrialmembranepotentialofCD3~-CD19~+Bcellswas1785.60±493.54 in the control group and 1372.78±334.73 in the BaP group,which was significantly lower than that in the control group(P<0.01).After the last Administration for 14 weeks,the mitochondrial ROS fluorescence values was 158.39±47.76 in the control group and198.52±58.97 in the BaP group,which were higher than those in the control group(P<0.05);The further statistical analysis of mitochondrial ROS fluorescence values of mononuclear cells in mice and lung cancer groups showed that the normal group was 176.82±78.68,and the lung cancer group was 217.40±80.43.Compared with the normal group,the lung cancer group decreased,but there was no statistical difference(P>0.05).The mitochondrial membrane potential of peripheral blood mononuclear cells was 1195.30±232.80 in the control group and 953.95±232.57 in the BaP group,which was lower than that in the control group(P<0.01).In the BaP group,the mitochondrial membrane potential of monocytes was1008.92±217.54 in unobtained lung cancer mice and 903.55±238.90 in the lung cancer mice,which was higher than that in unobtained lung cancer mice,but it had no statistical difference(P>0.05).The ATP content of peripheral blood mononuclear cells in the control group was 16.65±5.73 and12.27±3.69 in the BaP group,which was significantly lower than that in the control group(P<0.01).The ATP value of the mononuclear cells in unobtained lung cancer mice in the BaP group was 13.72±3.30,and9.82±3.16 in the lung cancer mice.The ATP content was significantly lower than that in in unobtained lung cancer mice and was statistically different.At the same time,it was found that the mitochondrial membrane potential of CD3~+CD19~-T cells was 355.57±93.58 in the control group and 312.35±86.86in the BaP group,which was lower than that in the control group(P<0.05);In the BaP group,the T-lymphocyte count was 340.27±87.53 in in unobtained lung cancer mice and 286.75±79.60 in the lung cancer mice,which was lower than that in unobtained lung cancer mice and had a statistically significant difference(P<0.05).In the control group,the membrane potential of CD3~-CD19~+B cells in the peripheral blood was1501.82±535.31,and in the BaP group was 1122.42±283.06.Compared with the control group,the B lymphocyte membrane potential in the BaP group was significantly reduced with statistical significance(P<0.01);In the BaP group,the mitochondrial membrane potential of B lymphocytes in unobtained lung cancer mice was 1210.99±312.10,and that of the lung cancer mice was 1041.23±231.17,which was lower than that in unobtained lung cancer mice(P<0.05).The above results showed that the mitochondrial ROS content in peripheral blood mononuclear cells increased,the mitochondrial membrane potential decreased,and the ATP synthesis decreased after the last administration for 6 weeks before the occurrence of lung cancer,resulting in decreased mitochondrial function and decreased immune cell energy synthesis in immune cells.And these changes preserve until lung cancer occurs.This indicates that BaP has caused a decrease in mitochondrial function of peripheral blood immune cells before BaP induces lung cancer in animals.In addition to carcinogenic effect of BaP,BaP-induced decline in mitochondrial function in peripheral blood immune cells is one of the main reasons to induce lung cancer.In summary,compared with normal people,lung cancer patients have decreased mitochondrial function and decreased immune cell energy synthesis.At the same time,after the last Administration for 6 weeks and 14weeks after the last administration,the immune function of the BaP mice was reduced compared with the normal group,and the immune function of the body may be damaged.It is one of the important factors that cause tumor development.This study provides a new idea for revealing the mechanism of lung cancer,and provides a theoretical basis for the early diagnosis and treatment of lung cancer. |
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