| Objective: Cerebral infarction is a disease to bring a heavy economic burden to the society and the families of the patients because of its high morbidity, mortality and disability rate. Since 2009 we have done a series of research on combined use of atorvastatin and propucol to brain infarction and cerebral protection mechanism. 9 SCI papers have been published in Brain Research, Neurosciense journal Letters etc. Our Research includes atorvastatin, propucol test by adjusting the expression of signaling pathways, such as Prx2, Foxo3 a, Nrf2, p-JNK, p-c-Jun, NF-?B, HMGB1, HMGB1 receptor(RAGE and TLR4), 12/15-LOX, p38 MAPK and c PLA2 and protection against ischemic Brain injury. These signaling pathways play important roles in the field of anti-inflammatory and antioxidant stress, becoming the hot topics in the study of ischemic stroke. The inflammatory reaction and oxidative stress plays an important role in brain tissue necrosis and ischemia, and is also the main cause of the secondary injury. Therefore, reducing inflammation and oxidative stress damage has become an important method in treatment of acute cerebral infarction. Anti-inflammatory and antioxidant stress treatment atrracted a lot of scholars' attention. Joint application of anti-inflammatory and antioxidant drug may bring new breakthrough for the treatment of cerebral infarction. Recent research shows that Ox-LDL is a low density lipoprotein(LDL) oxidation modification in the body, which formed the reaction and oxidative stress in the body. There is a close relationship between inflammation and endothelial damage. With CRP being a classic inflammatory markers, rise of the C-reactive protein levels and pathological changes of cerebral arteries of acute damage and deterioration of development have a close relationship?2014 AHA/ASA Guideline(Guidelines for the Early Management of Patients With Acute Ischemic Stroke) stated that brief withdrawal of statins during the acute period was associated with increased odds of death or dependency at 3 months.100 cases of atherosclerotic cerebral infarction patients treated with atorvastatin and probucol 3 months were included in our study, and the effects of atorvastatin and probucol on blood-lipoids,ox- LDL and high-sensitivity C-reactive protein(hs-CRP) levels were studied. We aimed to provide more effective and reasonable treatment strategy for the prevention and treatment of atherosclerotic cerebral infarction.Methods:100 patients(male: 51 cases, female: 49 cases; age: 59.34±10.56 years) who were first onset atherosclerotic cerebral infarction and hospitalized in the fifth neurology department of the first hospital of Shijiazhuang from August 2014 – February 2015 were included in the study. The patients were all at acute stage of the disease(<72hs)and diagnosed according to the revision version of the fourth national Cerebrovascular Disease Conference. The cerebral infarction was confirmed by CT or MRI examination. All the patients suffered carotid atherosclerosis that confirmed by carotid color duplex. According to the TOAST classification, the cases of cardiac infarction, other causes of cerebral infarction and unknown causes of cerebral infarction were excluded in the study. The patients were randomly divided into group A(atorvastatin treated group, n=49) and group A+P(atorvastatin and probucol treated group, n=51). The blood-lipoids ox-LDL and hs-CRP levels were measured before treatment and 3 months after treatment, and the NIHSS scores were evaluated t in the meantime. 30 cases of healthy people from the physical examination center were recruited as the control group(male: 17 cases,female: 13cases; age: 60.12±11.36 years). All the patients in the treatment group were confirmed atherosclerosis by carotid color duplex. The patients who suffered past medical history as cerebral infarction, atrial fibrillation, not stable type angina pectoris, myocardial infarction in the past 6 months, lower extremity vascular disease, severe liver and kidney disease, malignant tumor, severe infection, immune system disease and treated with following medicine as antioxidant agent, statins, hormone or immunosuppressive agents were excluded in the study. On the basis of the routine treatment, the patients of group A were treated with atorvastatin(20mg,qn), and the patients of group A+P were treated with atorvastatin(20mg,qn) and probucol(500mg, bid). 6ml fasting venous blood were drew for ox-LDL, hs-CRP, blood lipids, liver function and myocardial enzyme tests.Ox-LDL was tested by the enzyme labeled polyclonal antibody sandwich method, and the kit was provided by Shanghai Rong Sheng biological agent company. Hs-CRP was tested by the immune projection method, and the kit was provided by the RB company of United States. The data was analyzed by the automatic biochemical analyzer in our hospital. All the patients in the treatment groups were confirmed atherosclerosis by carotid color duplex, and the NIHSS scores were evaluated on the on the admission day. Ox-LDL, hs-CRP, blood lipids, liver function and myocardial enzyme were tested after 90 days treatment, and the NIHSS scores were evaluated in the meantime.The statistical analysis was performed using SPSS software version 21.0 All measurement data were presented as x ±S. The enumeration data were analyzed by x2 test, and the measurement data were analyzed by t test. Variance analysis was used to compare between groups.Results:1 The serum ox-LDL level was statistically high in the case group compared to the control group(P<0.05).2 The serum hs-CRP level was statistically high in the case group compared to the control group(P<0.05).3 The serum lipoids level,ox-LDL level,hs-CRP level and NIHSS scores was no significant difference before treatment(P>0.05). While after 3-month treatment the serum TG level,TC level,LDL-C level,ox-LDL level?hs-CRP level and NIHSS scores were significantly decreased in the group A and the group A+P compared to before the treatment.(P<0.05). The serum HDL level was significantly increased in the group A and the group A+P compared to before the treatment.(P<0.05).While there was no significant difference in the serum Apo B level compared to before the treatment.(P>0.05).4 After 3-month treatment, there was significant difference in the decreased levels of TG,TC,LDL-C,NIHSS score and ox-LDL between in the group A + P and the group A(P < 0.05).There was no significant difference in the decreased levels of hs-CRP and increased levels of HDL between the A group and A+P group.(P > 0.05).5 There was no significant difference in the safety index between the two groups after treatment(P>0.05).Conclusion:In the cerebral infarction acute phase, serum ox-LDL level, hs CRP level increased significantly. After 3-month treatment, there was significant difference in the decreased levels of TG,TC,LDL-C,ox-LDL and NIHSS score between in the group A+P and the group A.There was no significant difference in the decreased levels of hs-CRP ang increased level of HDL between the A group and A+P group. Combination treatment with atorvastatin and probucol did not increase the adverse reaction and damage to liver and kidney function compared to the treatment with atorvastatin alone, which suggested that atorvastatin combined with probucol can enhance the effects of lipid-lowering, anti-oxidation, anti-inflammation and significant brain protection and combination treatment with atorvastatin and probucol is safe. |
PDF Full Text Request