Objective: To explore the relationship between hypoxic pulmonary arterial smooth muscle cells(PASMCs)proliferation, apop-tosis and mitogen-activated protein kinases(MAPK) signal pathway in rats.
Methods: PASMCs were obtained from male SD rats by the enzyme digestion method and primarily cultured; PASMCs were identified through two methods:immunofluorescence staining and light microscopy; the 4~6th generation PASMCs of logarithmic growth state of good growth period were selected, and randomly divided into 7 groups:normoxic con-trol group (N), hypoxia group (H), DMSO group (D), extracellular signal-regulated kinase1/2(ERK1/2) inhibitor-U0126 group (U) and p38MAPK inhibitor-SB203580 group (S), the p38MAPK activator-Anisomycin group (A), the ERK1/2 activator-Staurosporine Aglycone group (SA). When all the models were completed, the all groups joined the CCK-8 to measure cell proliferation; cell apoptosis of each group was detected by TUNEL kit after the modeling.
Results: Compared with N group, the expression of OD value in H group was up-regulated (0.990 ±0.041 vs 1.143 ±0.033,P < 0.01). There was no statistical significance on PASMCs apoptosis index(AI) in H group (4.913 ±0.451 vs 5.452 ±0.557, P > 0.05); Compared With H group, there were no statistical significance on the expression of PASMCs OD value and apoptosis index(AI)in D group (1.143 ±0.033 vs 1.142 ±0.049,5.452 ±0.557 vs 5.402 ±0.651,P > 0.05); the expression of OD value in U group was down-regulated, and the expression of AI was up-regulated (1.143 ±0.033 vs 0.985 ±0.078, 5.452 ±0.557 vs 10.145 ±2.545, P < 0.01); the expression of OD value in S group was up-regulated, and the expression of AI was down-regulated (1.143 ±0.033 vs 1.295 ±0.039, 5.452 ±0.557 vs 3.093 ±0.409, P < 0.01); the expression of OD value in A group was down-regulated, and the expres-sion of AI was up-regulated (1.143 ±0.033 vs 0.347 ±0.067, 5.452 ±0.557 vs 25.753 ±1.262, P < 0.01); the expression of OD value in SA group was up-regulated, and the expression of AI was down-regulated (1.143 ±0.033 vs 1.685 ±0.100, 5.452 ±0.557 vs 1.700 ±0.095, P < 0.01).
Conclusions: The regulation of PASMCs' proliferation and apoptosis under hypoxia condition have a relationship with the participation of MAPK signal pathway.
Keywords: ERK1/2; PASMCs; apoptosis; hypoxia; p38MAPK; proliferation; rat.