p110δ/α小分子抑制剂在小鼠心脏移植急性排斥反应中作用机制

Mechanism of p110δ/α inhibitors in acute rejection of heart transplantation in mice

目的研究p110α/δ小分子抑制剂A66/CAL^-101对小鼠心脏移植模型急性排斥反应的影响及作用机制。方法建立小鼠心脏移植模型,随机分为同系移植组、急性排斥组、p110α抑制剂干预组(A66组)、p110δ抑制剂干预组(CAL^-101组)。A66组、CAL^-101组建模后腹腔注射1 mg·kg^-1A66、CAL^-101,同系移植组、急性排斥组腹腔注射1 mL·kg^-1二甲基亚砜(DMSO),每天1次。取6只小鼠连续给药7 d后,用酶联免疫吸附(ELISA)法检测外周血干扰素-γ(INF-γ)、白细胞介素-10(IL^-10)、白细胞介素-17(IL^-17)、白细胞介素-21(IL-21)含量。结果 A66组,CAL^-101干预组,急性排斥组INF-γ分别为(182.45±25.66),(256.84±36.65),(415.68±58.94)pg·mL^-1,IL^-17分别为(11.62±1.58),(13.64±1.74),(18.69±2.64)pg·mL^-1,IL-21分别为(28.64±3.53),(36.54±4.11),(54.68±6.55)pg·mL^-1,IL^-10分别为(410.52±45.52),(320.51±38.69),(223.54±45.36)pg·mL^-1,差异均有统计学意义(P<0.05,P<0.01)。结论 p110α/δ小分子抑制剂A66/CAL^-101能延长移植心脏存活时间,改善心肌细胞水肿、炎性细胞浸润等现象。

Objective To investigate the mechanism of p110δ/α inhibitors in acute rejection of heart transplantation in mice. Methods Mice were made into heart transplantation model and were randomly divided into syngeneic transplantation group, acute rejection group, p110α inhibitor intervention group(A66 group), and p110δ inhibitor intervention group(CAL^-101 group). Mice in A66 group and CAL^-101 group received the 1 mg·kg^-1 A66(ip) and 1 mg·kg^-1 CAL^-101(ip) respectively. Mice in syngeneic transplantation group and acute rejection group received 1 mL·kg-1 dimethyl sulfoxide(DMSO) once a day. 6 mice in each group were administrated continually for 7 d, then the levels of interferon-γ(INF-γ), interleukin-10(IL^-10), interleukin-17(IL^-17) and interleukin-21(IL-21) in peripheral blood were detected by enzyme-linked immunosorbent assay(ELISA). Results The levels of INF-γ in the peripheral blood of A66 group, CAL^-101 group, acute rejection group were(182.45±25.66),(256.84±36.65),(415.68±58.94) pg·mL^-1, IL^-17 were(11.62±1.58),(13.64±1.74),(18.69±2.64) pg·mL^-1, IL-21 were(28.64±3.53),(36.54±4.11),(54.68±6.55)pg·mL^-1,IL^-10 level in the peripheral blood were(410. 52 ± 45. 52),(320. 51 ± 38. 69)(223. 54 ± 45. 36)pg·mL^-1,all with statistic difference(P < 0. 05,P < 0. 01). Conclusion P110α/δ inhibitor A66/CAL^-101 can prolong the survival time of transplanted heart and ameliorate the myocardial cell edema and inflammatory cell infiltration.