Study Of Effects Of Probucol Combined With Atorvastatin On Atherosclerosis

Objective:To observe the effects of Probucol combined with Atorvastatin and Atorvastatin on Atherosclerosis.Methods:18 New Zealand rabbits were divided into Control group (named A group, n=3) and High Fat Diet (HFD) group (named X group, n=15) randomly. HFD group was fed up with 2% cholesterol for 6 weeks. After 6 weeks, HFD group was divided into 3 groups by weight randomly. The names of group were High Fat group (named B group, n=3), Atorvastatin group (high fat with Atorvastatin 5mg/kg.d,qn, named C group, n=6) and Association group (high fat with Atorvastatin 5mg/kg.d,qn and Probucol 0.25g/kg.d.bid, named D group, n=6). These groups were interference by drugs and high fat diet synchronously. The blood fat was examined at baseline,6 weeks and 12 weeks. After 12 weeks, HE and oil red "O" of thoracic aorta, the thickness of endomembrane and tunica media, the area of atheromatous plaque and IL-6 levels were examined.318 ACS patients (192 male patients and 126 female patients) were divided into Association group (n=147) and Control group (n=171) randomly. After 12 weeks, Ox-LDL and Hs-CRP were examined individually. As for the sub-group combined with Type 2 Diabetes Mellitus, blood fat, sub-type of HDL and ApoA I were examined before and after treatment. SNYTAX was calculated from 20 patients who were selected randomly from PCI patients. We also monitored the adverse reaction of drugs during the treatment.Result:1. At baseline, there were no obvious differences (P>0.05) in the value of TC, TG, HDL and LDL. After 6 weeks, the blood fat level of B, C and D group was significant higher than of A group (P<0.05), there was no obvious difference between B, C and D group (P>0.05). After 12 weeks, there was difference between A, B, C and D group in TC, TG, HDL and LDL levels. There was significant difference between C and D group compared with 6 weeks before in TC, TG, HDL and LDL levels.(P<0.05). There was also obvious difference between C and D group in TC, HDL and LDL levels (P<0.05).2. In HFD group, there were typical lipid stripe and localized plaque in aorta, and the expression of IL-6 was significant. Compared with B group, there was obvious reduction of increased thickness of aortic tunica intima and area of atheromatous plaque in C group (P<0.05) and D group (P<0.01). There were reductions of IL-6 levels in C and D group, and the reductions between C and D were obvious (P<0.05). D group was much more significant.3. After 12 week's treatment of ACS patients, the values of Ox-LDL and Hs-CRP in Association group were significantly lower than in Control group (409.3±42.1 vs 487.2±65.2ug/l,p<0.01; 3.28±1.11 vs 3.93±1.76mg/l,p<0.01).4. As for the sub-group combined with Type 2 Diabetes Mellitus, the level of TG in Association group was obviously lower than in Control group. The level of HDL was obviously lower than pre-treatment (P<0.05), and the level of HDL3 and HDL3/HDL was significantly higher (P<0.05).In Control group, there was obvious difference in level of HDL (P<0.05), but there was no significant change in level of HDL3 and HDL3/HDL (P>0.05).5. After 6 month's treatment, the value of SYNTAX in Association group was lower than Control group (P<0.05).6. The security index in both groups had no obvious change (P>0.05).Conclusion:1. There was lower level of TC, LDL and TG in Association group. There was effect including reducing area of atheromatous plaque, alleviating inflammatory reaction of plaque and reducing level of Ox-LDL and Hs-CRP. It had proved that Probucol combined with Atorvastatin could reinforce fat regulation, strengthen anti-inflammatory action and antioxidation, and benefit reversion of atheromatous plaque.2. It has showed that Association group had higher HDL3 level and proportion of HDL3/HDL. It could optimize sub-type of HDL, and promote antiport of cholesterol.3. There was obvious change of SYNTAX value in Association group after operation. It showed that Probucol combined with Atorvastatin could benefit in preventing restenosis in ACS patients after PCI operation.4. There was no adverse reaction and impairment of liver and renal in Association group. It proved that drug combination was security.