ABSTRACT
Objective To explore the effects of matrine on apoptosis and nuclear factor(NF)-κBp65 activity of HL-60 cells induced by pirarubicin (THP).Methods Effects of the apoptosis:the HL-60 cells in blank control group were cultured 14 hours with RPMI 1640; groups of different concentration drugs:matrine:0.1 μmol/L,1.0 μmol/L,10.0 μmoL/L and THP:1.0 μmol/L,10.0 μmol/L,100.0 μmol/L.The apoptosis of HL-60 cells were tested by fluorescence double colour painting and flow cytometry (FCM).The NF-κBp65 activity of HL-60 cells were determined by FCM.Results The rates of apoptosis of HL-60 cells were (7.14 ± 2.95) ％,(12.34 ± 2.55) ％,(19.3 ±2.31)％ and (31.78 ±4.31)％,(47.25 ±5.27)％,(56.49 ±1.59)％ in matrine 0.1 μmol/L,1.0 μmol/L,10.0 μmol/L and THP 1.0 μmoL/L,10.0 μmol/L,100.0 μmol/L groups,compared to blank control group (6.46 ± 1.45) ％,there were significant difference (F =257.72,677.19 ; all P ＜ 0.001) ; (70.17 ± 5.68) ％ in matrine 0.1 μ mol/L +THP 1.0 μ moL/L group[vs the THP 1.0 μmoL/L group (31.78 ±4.31)％,(t =38.94,P＜0.001)].The rates of NF-κBp65 activity of HL-60 cells in matrine 0.1 μmol/L,1.0 μmol/L,10.0 μmol/L and THP 1.0 μmol/L,10.0 μmol/L,100.0 μmol/L groups were(8.34 ± 1.52)％,(7.11 ± 1.29)％,(4.78 ±0.31)％ and (16.21 ± 1.20) ％,(23.98 ± 3.21) ％,(32.44 ± 2.89) ％,with the control group (8.44 ± 2.20) ％,there were significant difference(F =65.35,P ＜ 0.001 ; F =674.11,P ＜ 0.001) ; (12.01 ± 2.27) ％ in matrine 0.1 μmol/L + THP 1.0 μmol/L group [with (16.21 ± 1.20) ％ of THP 1.0 μmol/L group(t =21.42,P ＜ 0.001)].Conclusions The apoptosis of HL-60 cell is induced by matrine and pirarubicin in a dose-dependent manner.NF-κBp65 activity of HL-60 cell is inhibited by matrine and increased by pirarubicin in a dose-dependent manner.Matrine can enhannce the effect of induction by pirarubicin of apoptosis of HL-60 cell,and decrease activity of NF-κBp65 by pirarubicin.
ABSTRACT
Objective The purpose of this paper is to study the relationship between blood concentration and brain tissue drug concentration by different dose of TMX chemotherapy acute lymphoblastic leukemia in mice. Methods 4 weeks, health Kun Ming mice 80: establishment acute lymphoblastic leukemia mice model,20 mice were randomly selected to take the femur bone marrow biopsy bone marrow OK for model verification; the remaining 60 acute lymphoblastic leukemia mice were allocated randomly 6 groups of 10 mice in each group, respectively A, B, C, D, E, F groups. And collected blood 0.5 ml and brain tissue 0.4 g individually at 0.5 hour in every group. We used supernatant of centrifugation blood and brain homogenate to detected drug concentration by fluorescence polarization immunoassay. Results The mean blood concentration of MTX of six groups A, B, C, D, E, F are (39.08±5.18) μmol/L, (15.86±1.02)μmol/L, (8.67± 5.43)μmol/L, (68.29±5.19)μmol/L, (29.55±6.22)μmol/L, (13.98±1.12)μmol/L, respectively. Compared the mean blood concentration of MTX of each group there are statistical significance (P<0.05). The mean concentration of MTX of six groups in brain tissue are followed by A group (1.05±0.26)μmol/L, B group (0.61±0.25)μmol/L, C group (0.48±0.25)μmol/L, D group (2.07±0.35)μmol/L, E group (1.27±0.21)μmol/L, F group (0.59±0.69)μmol/L. Compared the mean concentration of MTX of each group in brain tissue there are statistical significance (P<0.05). MTX concentration in blood and in brain tissue of correlation coefficient followed by 0.82, 0.75, 0.19, 0.81, 0.55, 0.43. Conclusion The chemotherapy acute lymphoblastic leukemia mice of HDMTX scheme, the peak of blood concentration and brain tissue drug concentration is come after injected MTX 0.5 hour, MTX 5 g/m~2 is better permeation blood-brain barrier and more easy make brain tissue drug concentration to reach effectively therapeutic concentration than MTX 3 g/m~2.
