瑞舒伐他汀通过抑制PI3K/AKT信号通路活性缓解小鼠颈动脉粥样硬化

Experimental study of rosuvastatin in alleviating carotid atherosclerosis by inhibiting PI3K/Akt signal pathway activity

目的探讨瑞舒伐他汀缓解小鼠颈动脉粥样硬化的机制及相关信号通路。方法将75只Apo E^-/-小鼠随机分为5组,采取不同的干预措施,分别为对照组、颈动脉粥样硬化模型组、瑞舒伐他汀低剂量组、中剂量组、高剂量组。检测5组小鼠的血脂相关指标;实验结束后,处死小鼠,采用PCR技术,检测各组小鼠颈动脉组织中MMP-2 mRNA、MMP-9 mRNA的表达差异;采用Western-blot检测颈动脉组织中p-PI3K蛋白、p-AKT蛋白、PI3K蛋白、AKT蛋白的表达水平。结果①与模型组相比,3个瑞舒伐他汀治疗组小鼠的TC、TG、LDL-C水平明显下降,HDL-C明显升高(P<0.05)。3个治疗组小鼠颈动脉总面积与模型组相比差异无统计学意义(P<0.05),但斑块面积显著较小(P<0.05),且高剂量组的斑块面积最小。②对照组小鼠颈动脉组织中MMP-2的阳性率较低,模型组的MMP-2的阳性率及染色强度明显较高。低、中、高剂量组的的染色阳性率及染色强度较模型组有明显下降。③模型组小鼠颈动脉组织中MMP-2 mRNA、MMP-9 mRNA的相对表达量显著最高,低剂量组次之,高剂量组表达水平最低。Western-blot检测结果趋势与RT-PCR一致。④与对照组相比,模型组小鼠颈动脉组织中p-PI3K蛋白、p-AKT蛋白表达量明显升高(P<0.05)。与模型组比较,瑞舒伐他汀3个治疗组的小鼠颈动脉组织中p-PI3K蛋白、p-AKT蛋白表达量逐渐下降。结论瑞舒伐他汀可通过抑制PI3K/AKT信号通路活性对颈动脉粥样硬化小鼠发挥保护作用。

Objective To investigate the mechanism and signal pathway of rosuvastatin in alleviating carotid atherosclerosis. Methods 75 ApoE^-/-were randomly divided into control group,carotid atherosclerosis model group,low dose group,middle dose group and high dose group. At the end of the experiment,the rats were killed and the expression of MMP-2 mRNA and MMP-9 mRNA in the common carotid artery tissues of each group were detected. The expression levels of p-PI3 K protein,p-Akt protein,PI3 K protein and Akt protein were detected by Western blot. Results ①Compared with the model group,the levels of TC,TG and LDL-C in the three treatment groups decreased significantly,while HDL-C increased significantly(P<0.05). ②In the control group,the positive rate of MMP-2 was lower than that in the model group. The positive rate and staining intensity of the treatment group were significantly lower than that of the model group. ③The relative expression of MMP-2 mRNA and MMP-9 mRNA in the model group was the highest,followed by the low dose group and the high dose group. The trend of Western blot was consistent with RT-PCR. ④Compared with the control group,the expression of p-PI3 K protein and p-Akt protein in the model group was significantly increased(P<0.05). Compared with the model group,the expression of p-PI3 K protein and p-Akt protein in the carotid tissues of the three treatment groups decreased gradually. Conclusion Rosuvastatin can play a protective role in rats with carotid atherosclerosis by inhibiting the activity of PI3 K/Akt signal pathway.