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目的探讨普罗布考联合阿托伐他汀治疗对脑梗死患者血清ox-LDL、MMP-2、MMP-9水平的影响。方法急性脑梗死患者120例,入院查颈动脉彩超提示存在AS斑块,男68例,女52例,平均年龄(74±15)岁(39～84岁),并随机分为两组,第一组男35例,女25例,平均年龄(73±16)岁(39～83岁),予阿托伐他汀(20 mg/d);第二组男33例,女27例,平均年龄(76±18)岁(41～84岁),予阿托伐他汀(20 mg/d)、普罗布考(500 mg/d)联合治疗;两组患者分别于治疗前、治疗后6、12、24月检测血清氧化低密度脂蛋白(ox-LDL)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)水平。结果 (1)两组治疗前ox-LDL水平分别为(781.42±32.56)、(777.38±208.91)ng/ml,无显著差异;治疗后6月第一组ox-LDL水平无明显变化(790.24±229.33)ng/ml,而第二组有较明显的下降(626.4±189.78)ng/ml(P<0.05);12月时第一组ox-LDL水平稍有下降(760.89±200.37)ng/ml,但无明显差异(P>0.05),第二组ox-LDL水平进一步明显下降(601.82±181.64)ng/ml(P<0.01);24月时两组继续保持12月时水平(762.53±212.11)、(612.43±193.49)ng/ml。(2)两组治疗前MMP-2水平分别为(186.62±61.74)、(194.78±63.22)ng/ml,MMP-9水平分别为(309.57±112.26)、(324.98±109.45)ng/ml,均无显著差异;治疗后6月均明显下降,即MMP-2分别为(127.94±38.12)、(128.67±40.09)ng/ml,MMP-9分别为(238.34±73.59)、(209.67±68.45)ng/ml,且第二组MMP-9水平下降尤甚(P<0.01);12月时较6月时有轻度上下波动,即MMP-2水平分别为(131.73±37.69)、(116.32±29.85)ng/ml,MMP-9水平分别为(208.93±64.33)、(218.58±70.22)ng/ml;24月时较12月时有所下降,即MMP-2水平分别为(110.88±30.53)、(87.68±25.76)ng/ml,MMP-9水平分别为(201.75±80.07)、(172.93±58.23)ng/ml,且第二组较第一组下降更显著(P<0.01)。结论稳定斑块是治疗脑梗死动脉粥样硬化的重要而长远的策略,普罗布考联合阿托伐他汀可分别从降低低密度脂蛋白(LDL)、抑制ox-LDL的形成,降低血液循环中的MMP-2、MMP-9水平等途径多方位、多靶点地起到抗AS作用,可作为缺血性脑卒中二级预防中动脉粥样硬化新的干预途径。
Objective To investigate the effects of probucol combined with atorvastatin on serum ox-LDL, MMP-2 and MMP-9 in patients with cerebral infarction. Methods One hundred and twenty patients with acute cerebral infarction were examined by carotid ultrasonography. There were 68 males and 52 females with a mean age of (74 ± 15) years old (39-84 years old), and were randomly divided into two groups A group of 35 males and 25 females, mean age (73 ± 16) years (39 to 83 years), to atorvastatin (20 mg / d); the second group of 33 males and 27 females, mean age (76 ± 18) years old (41-84 years old) were treated with atorvastatin (20 mg / d) and probucol (500 mg / d). Before and after treatment, Serum levels of ox-LDL, MMP-9 and MMP-2 were measured in 24 months. Results (1) The levels of ox-LDL before treatment in the two groups were (781.42 ± 32.56) and (777.38 ± 208.91) ng / ml, respectively. There was no significant change in ox- 229.33) ng / ml, while the second group had a significant decrease (626.4 ± 189.78) ng / ml (P <0.05). The level of ox-LDL in the first group decreased slightly at the month of December (760.89 ± 200.37) ng / ml , But there was no significant difference between the two groups (P> 0.05). The level of ox-LDL in the second group was significantly decreased (601.82 ± 181.64) ng / ml (P <0.01) ), (612.43 ± 193.49) ng / ml. (2) The levels of MMP-2 in the two groups before treatment were (186.62 ± 61.74) and (194.78 ± 63.22) ng / ml respectively, and the levels of MMP-9 were (309.57 ± 112.26) and (324.98 ± 109.45) ng / (127.94 ± 38.12) and (128.67 ± 40.09) ng / ml, respectively. The MMP-9 levels were (238.34 ± 73.59) and (209.67 ± 68.45) ng / ml, especially in the second group (P <0.01). The level of MMP-2 in the second month was slightly higher than that in the sixth month (131.73 ± 37.69), (116.32 ± 29.85 (208.93 ± 64.33) and (218.58 ± 70.22) ng / ml, respectively. The levels of MMP-2 in 24 months decreased from 110.88 ± 30.53, (87.68 ± 25.76) ng / ml and MMP-9 levels were (201.75 ± 80.07) and (172.93 ± 58.23) ng / ml, respectively. The second group was more significant than the first group (P <0.01). Conclusions Stable plaque is an important and long-term strategy for the treatment of atherosclerosis in cerebral infarction. Probucol combined with atorvastatin can decrease the level of LDL, inhibit the formation of ox-LDL and decrease the blood circulation MMP-2, MMP-9 levels of multi-directional, multi-target play an anti-AS role, as secondary prevention of ischemic stroke secondary prevention of atherosclerosis intervention.