人白细胞介素10对血管紧张素II诱导的大鼠血管平滑肌细胞增殖的作用

Recombinant human interleukin-10 inhibits the vascular smooth muscle cell proliferation in rat stimulated by angiotensin II

目的 观察重组人白介素 10 (rhIL 10 )对血管紧张素Ⅱ (AngⅡ )刺激下离体大鼠胸主动脉血管平滑肌细胞增殖及对 p4 4 /p4 2丝裂素活化蛋白激酶的影响。 方法 体外培养大鼠主动脉血管平滑肌细胞 ,采用MTS/PES(methoxyphenyl tetrazoliumsalt/phenazineethosulfate)法确定血管平滑肌细胞的增殖状态。利用 p4 4 /p4 2磷酸化抗丝裂素活化蛋白激酶抗体的蛋白免疫印迹法测定丝裂素活化蛋白激酶蛋白的表达 ;对照组为未用AngⅡ刺激的血管平滑肌细胞。 结果 AngⅡ对大鼠血管平滑肌细胞增殖具有明显的刺激作用 (1 311± 0 2 0 1对 0 781± 0 2 36 ,P <0 0 5 )。rhIL 10单独应用对血管平滑肌细胞生长没有影响 (0 783± 0 170对 0 781± 0 2 36 ,P >0 0 5 )。在AngⅡ刺激下 ,1、10、10 0ng/ml的rhIL 10均可抑制血管平滑肌细胞的生长 (分别为 0 984± 0 172、 0 932±0 134、0 784± 0 0 97对 1 311± 0 2 0 1,P <0 0 5 )。AngⅡ对p4 4 /p4 2丝裂素活化蛋白激酶蛋白表达有显著的增强作用 (5 12± 78对 10 0 ,P <0 0 1) ,此作用可被rhIL 10抑制 (5 12± 78对 32 9± 5 9,P <0 0 1)。 结论 rhIL 10可抑制AngⅡ诱导的血管平滑肌细胞增殖及 p4 4 /p4 2丝裂素活化蛋白激酶蛋白的表达。

Objective Vessel injury provokes the release of angiotensin II that influences the proliferation and migration of vascular smooth muscle cells (VSMCs). T lymphocytes produced, interleukin 10 is of immunoregulatory function. The purpose of this study is to determine the effects of recombinant human interleukin 10 (rhIL 10) on the proliferation of isolated rat vascular smooth muscle cell and the activity of p44/p42 mitogen activated protein kinase (MAPK) promoted by angiotensin II. Methods Rat aortic VSMCs were cultured and treated with rhIL 10 or angiotensin II, and then co treated with rhIL 10 and angiotensin II. The proliferation was quantified by colormetric assay. The p44/p42 MAPK activity was evaluated by the immunobloting technique using anti p44/p42 phospho MAPK antibody. Results Compared with control group, angiotensin II stimulated significantly VSMCs proliferation(1 311±0 201 vs 0 781±0 236, P <0 05). The rhIL 10 alone showed no effect on the VSMCs growth(0 783±0 170 vs 0 781±0 236, P >0 05), but significantly inhibited VSMCs proliferation induced by angiotensin II at a dose of 1,10,100 ng/ml (0 984±0 172 , 0 932±0 134 , 0 784±0 097 vs 1 311±0 201, P <0 05,respectively). The p44/p42 MAPK activity was significantly enhanced by angiotensin II(512±78 vs 100, P <0 01) and this effect was inhibited by rhIL 10 (512±78 vs 329±59, P <0 01). Conclusions The rhIL 10 inhibits the rat aortic VSMCs proliferation and the phosphorylation of p44/p42 MAPK induced by angiotensin II.