普罗布考联合阿托伐他汀对脑梗死患者血清ox-LDL、MMP-2、MMP-9水平的影响

摘要

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 explore the effect of Probucol combinding with Atorvastatin on ox-LDL, MMP-2 and MMP-9 in scrum of stroke patients. Methods 120 acute cerebral infarction patients, who have atherosclerotic plaques examined by carotid artery color Dopplcr ultrasound at the time of admission, including 68 males and 52 females and the average age were 74 15 yeares (39-84 years). They were divided into 2 groups randomly. Group 1 containing 35 males and 25 females whose average age were (73 ± 16) ycarcs (39～83 years) was received Atorvastatin(20 mg/L) ; Group 2 containing 33 males and 27 females whose ageragc age were (76 ± 18) ycarcs (41～84 ycarcs) was received Atorvastatin(20 mg/L) combinding with Probucol (500 mg/L). The concentration of scrum oxidatively modified lowdensity lipoprotcin(ox-LDL) ,matrix metallo pro-teinases-9 (MMP-9) and matrix metallo proteinascs-2 (MMP-2) were detected respectively before treatment,6 months after treatment, 12 months after treatment and 24 months after treatment. The results were compared among groups. Results (1)Changes of ox-LDL level before and after treatment; the ox-LDL concentration in Group 1 and Group 2 were (781. 42 ± 32. 56) ng/ml and (777. 38 ± 208. 91) ng/ml and had no statistical difference; There were no rcmarkly changes of ox-LDL 6 months after treatment in Group 1 (790. 24 ± 229. 33)ng/ ml while there were apparently decrease in Group 2 (626. 4 ± 189. 78)ng/ml (P<0. 05). 12 months after treatment the ox-LDL level in Group 1 decreased a bit (760. 89 ± 200. 37)ng/ml with no difference (P>0. 05) ,and the ox-LDL level in Group 2 decreased continuously to (601. 82 ± 181. 64) ng/ml (P<0. 01) ; 24 months after treatment the ox-LDL level in two groups keep the same as those in 12 months after treatment (762. 53 ± 212. 11)ng/ml and (612. 43 + 193. 49) ng/ml. (2) Changes of concentration of MMP-2 and MMP-9: the MMP-2 level were (186. 62 ± 61. 74) ng/ml in Group 1 and (194. 78 ± 63. 22) ng/ml in Group 2 and the MMP-9 level were (309. 57 ±112. 26) ng/ml in Group 1 and (324. 98 ± 109. 45) ng/ml in Group 2 both before treatment. There were neither statistical difference in the two groups; The MMP-2 (127. 94 ± 38. 12) ng/ml in Group 1 and (128. 67 ± 40. 09) ng/ml in Group 2 and MMP-9 (238. 34 ± 73. 59) ng/ml in Group 1 and (209. 67 ± 68. 45) ng/ml in Group 2 level both decreased in 6 months after treatment especially MMP-9 in Group 2(P< 0. 01) ; Mild volatility arose in 12 months after treatment compared with in 6 months. The MMP-2 level were (131. 73 ± 37. 69)ng/ml and (116. 32 ± 29. 85) ng/ml and the MMP-9 level were (208. 93 ± 64. 33) ng/ml and (218. 58 ± 70. 22)ng/ml in the two groups respectively; The enzyme level decreased 24 months after treatment compared with 12 months. The MMP-2 level in were (110. 88 ± 30. 53)ng/ml and (87. 68 ± 25. 76)ng/ml and the MMP-9 level were (201. 75 ± 80. 07)ng/ml and (172. 93 ± 58. 23)ng/ml in those two groups respectively. The decrease of MMP-2 and MMP-9 in Group 2 was more notably than those in Group 1 (P<0. 01). Conclusions Stablizing vulnerable plaque is an important and long-term strategy in treatment of atherosclerotic plaques in stroke patients. Probucol combinding with Atorvastatin could anti-athcrosc-lcrosis through reducing the LDL level,inhibiting the forming of ox-LDL,decreasing the scrum concentration of MMP-2 and MMP-9 by multi-directions and multi-targets. It could be a new therapy of anti-atherosclerosis in secondary prevention from ischemic stroke.