辛伐他汀改善神经源性肺水肿大鼠血清孵育后肺微血管内皮细胞的生长

Simvastatin Improves the Growth of Pulmonary Microvascular Endothelial Cells Incubated in Serum of Neurogenic Pulmonary Edema Rat

目的观察辛伐他汀对神经源性肺水肿(NPE)大鼠血清孵育后肺微血管内皮细胞(PMECs)生长的影响及Bax和Bcl-2表达的影响。方法制备NPE大鼠模型的血清,将体外培养的大鼠PMECs随机分成正常对照组、NPE24 h组、NPE48 h组、辛伐他汀24 h组、辛伐他汀48 h组;NPE组予NPE大鼠模型的血清分别孵育24 h和48 h,辛伐他汀组在NPE大鼠血清孵育的基础上予1μmol/L辛伐他汀干预24 h和48 h。通过细胞计数法描记生长曲线观察各组细胞生长情况,Western-bolt和RT-PCR分别检测各组PMECs内Bax和Bcl-2蛋白与mRNA表达情况。结果 NPE24 h组及48 h组PMECs生长明显减慢,倍增时间延长,有大量漂浮的细胞碎片;辛伐他汀24 h组和48 h组PMECs数量显著增高。同正常对照组相比,NPE24 h组和48 h组PMECs内Bax蛋白和mRNA表达显著增高(P<0.05),而Bcl-2蛋白和mRNA表达降低(P<0.05)。与相应NPE组相比,辛伐他汀24 h组及48 h组Bax蛋白和mRNA表达显著降低(P<0.05),而Bcl-2蛋白和mRNA表达增高(P<0.05)。同辛伐他汀24 h组相比,辛伐他汀48 h组PMECs内Bcl-2蛋白和mRNA表达显著增高(P<0.05)。结论辛伐他汀可改善NPE大鼠血清孵育后PMECs的生长,其机制可能与上调Bcl-2和下调Bax表达有关。

Objective To observe the effect of simvastatin on the growth of pulmonary microvascular endothelial cells（ PMECs） incubated in the serum of neurogenic pulmonary edema（ NPE） rat and expression of Bax and Bcl-2 of PMECs. Methods The PMECs were randomly divided into five groups,the control group,NPE 24 h group,NPE 48 h group,simvastatin 24 h group and simvastatin 48 h group. The two NPE groups were incubated in rat serum for 24 h and 48 h respectively. The two simvastatin groups were treated with 1 μmol/L simvastatin,also incubated in rat serum for 24 h and48 h respectively. The cell growth in each group was determined by the cell growth curve of cytometry,while the expression of Bax and Bcl-2 was detected by Western-bolt and RT-PCR. Results In the NPE 24 h and NPE 48 h groups,the growth rate of PMECs was significantly decreased with increased doubling time and a large amount of floating cell debris. In the simvastatin 24 h and simvastatin 48 h groups,the number of PMECs increased significantly. The expressions of Bax was significantly upregulated（ P 0. 05）,while the expressions of Bcl-2 was significantly downregulated（ P 0. 05） in the NPE24 h and NPE 48 h groups when compared with that in the control group. The expressions of Bax was significantly downregulated（ P 0. 05）,while the expressions of Bcl-2 was significantly upregulated（ P 0. 05） in the simvastatin 24 h and simvastatin 48 h groups when compared with that in the control group. The expression of Bcl-2 of PMECs in the simvastatin 48 h group was significantly increased（ P 0. 05） compared to the simvastatin 24 h group. Conlusions Simvastatin improves the growth of PMECs incubated with serum of NPE rat. One of the corresponding mechanisms may be related to the upregulation of Bcl-2 and downregulation of Bax.