2010•The Chinese Journal of Clinical PharmacologyRequires access

Study on the relationship between resistant and expression of P-glycoprotein in lymphocytes induced by the low dose methylprednisolone

Yi Lin

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Abstract

Objective To investigate the relationship between resistant and expression of P-glycoprotein(P-gp) in lymphocytes induced by low dose methylprednisolone. Methods Venous blood of healthy people was obtained. The lymphocytes were separated and purified,and were stimulated with the low dose (2 μg·mL-1) methylprednisolone for 72 h to be take as the glucocorticoid resistance group. The control group cells were cultivated normally. The expression of P-gp was detected by flow cytometry. The glucocorticoid resistance multiple was detected by MTT. The lymphocytes were stimulated with 200 μg·mL-1 methylprednisolone and one group of lymphocytes with glucocorticoid resistance interfered by 5 μg·mL-1 verapamil at same time. AnnexinⅤ of the lymphocytes was valued by flow cytometry. Results The expression of P-gp in peripheral blood lymphocytes stimulated by low dose methylprednisolone was up regulated significantly compared with control group. The multiple of glucocorticoid resistance of glucocorticoid resistance group is (2.89±0.21). Stimulated with the 200 μg·mL-1 methylprednisolone,Annexin Ⅴ(%)of glucocorticoid resistance group decreased significantly compared with control group. The percent of Annexin Ⅴ(%)showed statistically significant negative correlation with P-gp(%). Verapamil could increase the sensitivity of methylprednisolone to induce the lymphocytes apopotosis. Conclusion The glucoglucocorticoid id resistant characteristic mediated by P-gp could be the one of the important mechanism of glucocorticoid resistance at the later period of clinical treatment.

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Objective To investigate the relationship between resistant and expression of P-glycoprotein(P-gp) in lymphocytes induced by low dose methylprednisolone. Methods Venous blood of healthy people was obtained. The lymphocytes were separated and purified,and were stimulated with the low dose (2 μg·mL-1) methylprednisolone for 72 h to be take as the glucocorticoid resistance group. The control group cells were cultivated normally. The expression of P-gp was detected by flow cytometry. The glucocorticoid resistance multiple was detected by MTT. The lymphocytes were stimulated with 200 μg·mL-1 methylprednisolone and one group of lymphocytes with glucocorticoid resistance interfered by 5 μg·mL-1 verapamil at same time. AnnexinⅤ of the lymphocytes was valued by flow cytometry. Results The expression of P-gp in peripheral blood lymphocytes stimulated by low dose methylprednisolone was up regulated significantly compared with control group. The multiple of glucocorticoid resistance of glucocorticoid resistance group is (2.89±0.21). Stimulated with the 200 μg·mL-1 methylprednisolone,Annexin Ⅴ(%)of glucocorticoid resistance group decreased significantly compared with control group. The percent of Annexin Ⅴ(%)showed statistically significant negative correlation with P-gp(%). Verapamil could increase the sensitivity of methylprednisolone to induce the lymphocytes apopotosis. Conclusion The glucoglucocorticoid id resistant characteristic mediated by P-gp could be the one of the important mechanism of glucocorticoid resistance at the later period of clinical treatment.

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Available abstract

Objective To investigate the relationship between resistant and expression of P-glycoprotein(P-gp) in lymphocytes induced by low dose methylprednisolone. Methods Venous blood of healthy people was obtained. The lymphocytes were separated and purified,and were stimulated with the low dose (2 μg·mL-1) methylprednisolone for 72 h to be take as the glucocorticoid resistance group. The control group cells were cultivated normally. The expression of P-gp was detected by flow cytometry. The glucocorticoid resistance multiple was detected by MTT. The lymphocytes were stimulated with 200 μg·mL-1 methylprednisolone and one group of lymphocytes with glucocorticoid resistance interfered by 5 μg·mL-1 verapamil at same time. AnnexinⅤ of the lymphocytes was valued by flow cytometry. Results The expression of P-gp in peripheral blood lymphocytes stimulated by low dose methylprednisolone was up regulated significantly compared with control group. The multiple of glucocorticoid resistance of glucocorticoid resistance group is (2.89±0.21). Stimulated with the 200 μg·mL-1 methylprednisolone,Annexin Ⅴ(%)of glucocorticoid resistance group decreased significantly compared with control group. The percent of Annexin Ⅴ(%)showed statistically significant negative correlation with P-gp(%). Verapamil could increase the sensitivity of methylprednisolone to induce the lymphocytes apopotosis. Conclusion The glucoglucocorticoid id resistant characteristic mediated by P-gp could be the one of the important mechanism of glucocorticoid resistance at the later period of clinical treatment.

Key concepts: Methylprednisolone, Glucocorticoid, Annexin, Flow cytometry, Verapamil, Prednisone, P-glycoprotein, Internal medicine

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