2019, 27(12):1045-1052.
Abstract:Aim To examine the effect of probucol on major advanced cardiovascular events (MACE) in patients with coronary artery disease undergone PCI. Methods Electronic databases, including PubMed, EMBASE, ScienceDirect and the Cochrane Central Register of clinical trial, CNKI database and Wan-Fang Database were used. The search items of“antioxidant”or“probucol” or “vitamin C”or “vitamin E” or “N-acetylcysteine”and “angioplasty”or “stent” and “randomized” were selected. RevMan 5.3 provided by the Cochrane was used to perform this analysis. Results In the enrolled 349 articles, there were 7 articles reporting MACE events in patients with coronary heart disease undergone PCI. There were 72 events in antioxidant group (72/2,0.5%). 111 events occurred in control group (111/4,1.4%). Compared to control group, antioxidant (probucol) group significantly decreased the incidence of MACE (RR 0.5,5%CI 0.51~0.84, P=0.0008). Compared with control group (86/2,4.3%), there was a lower rate of repeat revascularization in antioxidant group (52/2,4.8; RR 0.1,5%CI 0.44~0.83, P=0.002). No difference was observed in myocardial infarction death between groups (P=0.34,P=0.49). In addition, total cholesterol (TC) and low density lipoprotein- cholesterol (LDLC) were significantly decreased in probucol group when compared with control group (standard mean reduction SMD -0.8,5%CI -0.87~-0.49, P<0.00001; SMD -0.8,5%CI -0.46~-0.11, P=0.001, respectively). Conclusions Antioxidant probucol combined with conventional treatment significantly decreased the rate of MACE in patients with coronary artery disease undergone PCI. This benefit may be related to the improvement of repeat revascularization and lipid profile.
2017, 25(6):548-552.
Abstract:Aim To investigate the effect of probucol on the differentiation of inflammatory monocyte subsets and its potential mechanism. Methods The primary single cell suspension of spleen was prepared from 8 week old C57BL/6 mice. The differentiation of monocyte subsets was induced by 100 kU/L recombinant interferon-γ, then intervened with 5,0, 100 μmol/L probucol, in order to observe their effects on the differentiation of monocytes. The cells were stained with anti-CD11b-PE and anti-Ly-6C-FITC antibody, and the differentiation of monocyte subsets was detected by flow cytometry, then the data were analyzed by Flowjo software. Using intracellular cytokine staining and 2′,7′-dichlorofluorescein-diacetate probe, the level of reactive oxygen species (ROS) in monocyte subsets was detected by flow cytometry. NADPH oxidase activity in human monocytic cell line THP-1 was detected by using NADPH oxidase test kit. Results In a concentration dependent manner, 5,0, 100 μmol/L probucol inhibited the differentiation of Ly-6Chi inflammatory monocyte subsets in the spleen primary cells. The level of ROS in Ly-6C+ inflammatory monocyte subset was 2 times of that in Ly-6C- inflammatory monocyte subset. At the same time, 5,0, 100 μmol/L probucol inhibited the production of ROS in Ly-6C+ inflammatory monocyte subset in a concentration dependent manner. 100 μmol/L probucol significantly inhibited the activity of NADPH oxidase in THP-1 cells. Conclusion Probucol may interfere with the activity of NADPH oxidase, thereby inhibiting the differentiation of Ly-6Chi inflammatory monocyte subset and the production of ROS.
2016, 24(2):177-181.
Abstract:Aim To investigate influence of probucol combined with rosuvastatin on carotid atherosclerotic plaque, blood lipid, inflammatory factor in patients with cerebral infarction complicated with diabetes mellitus. Methods146 patients with cerebral infarction complicated with diabetes mellitus were selected in hospital from December 2011 to December 2013, who were randomly divided into two groups. 73 patients were treated with rosuvastatin as control group. 73 patients were treated with probucol combined with rosuvastatin as observation group. Carotid artery ultrasound results, serum lipid index changes, inflammatory factor changes, S100β and NIHSS score changes, adverse reactions were compared between two groups. Results After treatment, carotid artery intima-media thickness(CAIMT), carotid intimal plaque area, detection rate of vulnerable plaque, total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDLC), high sensitivity C reactive protein(hs-CRP), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), S100β, urine micro albumin, NIHSS score reduced significantly in two groups, while high density lipoprotein cholesterol(HDLC) increased significantly. CAIMT, carotid intimal plaque area, detection rate of vulnerable plaque, TC, TG, LDLC, hs-CRP, IL-6, TNF-α, S100β, urine micro albumin, NIHSS score in observation group were significantly lower than control group, while HDLC was significantly higher than control group. Differences were statistically significant(P<0.05). There were no significant difference between observation group and control group in incidence of adverse reactions(abnormal liver and kidney function, dizziness headache, rash, myalgia, nausea and vomiting, gastrointestinaltract reaction, P>0.05). Conclusion Probucol combined with rosuvastatin is an effective method in treatment of cerebral infarction complicated with diabetes mellitus, which can reduce carotid atherosclerotic plaque and improve blood lipid status, decrease inflammatory factor level and has high safety.
2015, 23(07):668-672.
Abstract:Aim To evaluate the protective effects and possible mechanisms of probucol on atherosclerosis in hyperlipidemic type 2 diabetic mice. Methods The hyperlipidemic type 2 diabetic (db/db-LDLR-/-) mice were generated by the cross between leptin receptor deficient (db/db) mice and low density lipoprotein receptor knockout (LDLR-/-) mice.8-week-old db/db-LDLR-/- mice were fed with high fat diet (HFD) mixed with 0.5% probucol,diabetic (db/db-LDLR-/-) and non-diabetic (LDLR-/-) control mice were fed with the same HFD without probucol addition.At 2 and 4 months after HFD,plasma lipids and glucose levels were measured.At 4 months after HFD,glucose tolerance and “en face” total aortic atherosclerotic plaque sizes were measured. Results Compared with type 2 diabetic HFD control group,probucol had strong protective effects on reducing plasma total cholesterol (TC),triglyceride (TG),glucose levels,improving glucose tolerance,and decreasing atherosclerotic lesions.Meanwhile,high density lipoprotein cholesterol (HDLC)/TC levels were unchanged. Conclusions Probucol had striking antiatherogenic effects under type 2 diabetic condition with hyperlipidemia.It might be an effective therapy in type 2 diabetic macrovascular disease.
2014, 22(10):1062-1066.
Abstract:Nowadays,cardio-cerebrovascular disease is a major cause of death in China.As a common pathogenic basis of coronary heart disease and stroke,atherosclerosis is a complex pathological process which is controlled by multiple factors.With its unique effects on anti-oxidation,anti-inflammation,cholesterol-lowering and improving endothelial function,probucol has been clinically used in preventing and treating atherosclerosis and coronary artery restenosis after angioplasty for decades.This review describes the situation and prospect in the research of probucol and its derivatives in treating atherosclerosis and restenosis from several aspects such as its mechanism,clinical application and the exploitation of its derivatives.
2014, 22(12):1207-1212.
Abstract:Aim To explore the effect of probucol on function of diatetic mice adipose tissue-derived stem cells (ADSC).Methods ADSC were isolated by mechanical separation and enzymatic digestion from nondiabetic and diabetic mice.The expression profiles of CD34,CD45,CD90 and CD105 were examined by flow cytometry.The ADSC were divided into 6 groups: control normal group,probucol normal group,control diabetic group,probucol diabetic group,high glucose normal group and probucol high glucose normal group.The proliferation and migration of ADSC was determined by WST-8 assay and transwell assay respectively.In addition,the mRNA and protein expression of vascular endothelial growth factor (VEGF),hepatocyte growth factor (HGF),and insulin-like growth factor-1(IGF-1) were determined by real-time PCR and ELISA analysis.The content of reactivated oxygen species (ROS) was also measured.Results The morphological feature of ADSC displayed fibroblast-like phenotype.The cells were positive for stem cells markers,including CD90 and CD105,and negative for CD34 and CD45,as shown by flow cytometry.Diabetic ADSC showed decreased proliferative potential and migration.In addition,the mRNA expression of VEGF,HGF and IGF-1 in diabetetic control group was obviously lower than that in nondiabetic control group.The contents of VEGF,HGF and IGF-1 on ADSC -conditioned medium in diabetic control group was also obviously lower than that in nondiabetic control group.Probucol promoted proliferation and migration of diabetic ADSC,and increase the mRNA expression of VEGF,HGF and IGF-1 in diabetetic ADSC.In addition,Probucol could increase contents of VEGF,HGF and IGF-1 in ADSC -conditioned medium in diabetic mice.Conclusion Our data indicate that diabetes alters ADSC intrinsic properties and impairs their function.Probucol can protect diabetic ADSC function of proliferation and migration,as well as releasing growth factors.
2013, 21(02):144-148.
Abstract:Aim To explore the possible mechanism by which probucol influenced cellular cholesterol efflux,and observe effects of serum from the mice pretreated by probucol on cellular cholesterol efflux. Methods Male C57BL/6J mice (n16) were randomly divided into two groups and treated with either vehicle or 0.5% probucol for 4 weeks respectively,the serum was collected and the lipids profile was detected by enzymatic method. Macrophages were loaded with ac-LDL and labeled with 3H-cholesterol,and treated with different concentrations of probucol,then the efflux of cholesterol was quantitated using the serum mentioned above as the acceptors. mRNA and membrane protein of the treated cells were extracted and used to evaluate the mRNA and protein expression of ABCA1,ABCG1 and SR-BI. Results More cholesterol efflux from the cultured macrophages was mediated by the serum from the mice treated with probucol for 4 weeks than those from the control mice. Probucol dose-dependently promoted cholesterol efflux and up-regulated the mRNA and protein expression of ABCG1 in macrophages,while had no effect on the mRNA and protein expression of SR-BI and ABCA1. Conclusions The serum from the mice pretreated with probucol markedly promoted macrophages cholesterol efflux. Probucol maybe promoted cholesterol efflux from the macrophages through increasing the expression of ABCG1 but had no relation to the expression of ABCA1 and SR-BI.
2011, 19(6):499-504.
Abstract:Aim To observe the effect of probucol on the atherosclerosis of experimental diabetic rats,and study its related mechanism. Methods Fourty rats were randomly divided into two groups,normal control group and the model group.Streptozotocin(STZ)was injected intraperitoneally to establish experimental diabetic rat models.Twenty-two rats became diabetes successfully and were randomly divided into two groups: diabetes group,probucol treatment group.After 8 weeks,all rats were executed,and the level of blood glucose,serum concentration of HDL,LDL,TC,TG,SOD,MDA,8-iso-PGF2α,platelet endothelial cell adhesion molecule-1(PECAM-1) were tested in each group.The structure of aorta and the thickness of intima was observed by the light microscope,and the expression of PECAM-1in aorta were assayed by immunohistochemistry. Results Compared with the normal control group,the blood glucose,body weight and water consumption of the model group increased significantly(P<0.01).The level of TC,TG and LDL were significantly increased(P<0.01),however HDL decreased.The thickness of intima in the light microscope was in creased(P<0.01),the structure of aorta revealed that intima was added thick and plaque formation mildly.Compared with the diabetes control group,the level of TC and LDL in probucol treatment group decreased significantly(P<0.01),but serum HDL and TG did not change significantly(P>0.05).The thickness of intima in the light microscope decrea sed significantly(P<0.01).Compared with the normal control group,the level of MDA,8-iso-PGF2α and PECAM-1 in diabetes group were significantly increased(P<0.01),but the level of SOD was much lower(P<0.01).Compared with the diabetes group,the level of MDA,8-iso-PGF2α and PECAM-1 in probucol treatment group decreased significantly(P<0.01),and the level of SOD increased significantly(P<0.01).The expression of PECAM-1 in probucol treatment group decreased significantly(P<0.01). Conclusions Probucol treatment can improve the atheromatosis of aorta in experimental diabetic rats.Its protection may be related to anti-oxidant and suppressiont of PECAM-1 expression in diabetic rats.
2011, 19(9):751-755.
Abstract:Aim To study the influence of probucol on the blood sugar uncontrolled type 2 diabetic mellitus patients with non-proliferative diabetic non-proliferative diabetic retinopathy(NPDR) about blood lipids,oxidative stress indicators,visual function and retinal morphology,so as to search treatment method for these patients.Methods 47 type 2 diabetes patients with 91 NPDR eyes and poor glycemic control at early stage were included.Patients were randomly divided into control and treatment groups:the control group treated by intensive therapy of blood glucose and blood pressure control,the treatment group were treated with the intensive therapy and probucol 0.375 g,2 times a day for 12 months.Before and after treatment,both groups of the patients had their blood lipids,serum level of the total antioxidant capacity(TAOC),superoxide dismutase(SOD),malondialdehyde(MDA),visual acuity,fundus,and fundus fluorescein angiography been checked.Results All 47 cases,91 eyes completed the study.Probucol obviously decreased levels of total cholesterol(TC),triglyceride(TG) and low density lipoprotein cholesterol(LDLC) in plasma of the patients.Levels of TAOC and SOD were improved significantly in the probucol group,while MDA decreased and the visual acuity improved significantly(P<0.01).The retinal capillary hemangioma,fundus bleeding and exudation,and macular edema were decreased significantly in patients of the probucol group(P<0.05).Probucol also has a role in reduction of capillary non-perfusion areas in the diabetic retina.Conclusions Probucol can not only regulate serum lipids of the poor glycemic controlled patients,but also has the action of improving antioxidant capacity.It can improve the visual function,ameliorate retinal’s microangiopathy,and decrease the incidence of macular edema.It means that probucol has a therapeutic effect in blood sugar uncontrolled NDPR patients.
2011, 19(11):923-925.
Abstract:Aim To compare the effects of probucol combined with atorvastatin and atorvastatin only on serum oxidized low density lipoprotein(ox-LDL)and ox-LDL antibodies(ox-LDL-Ab) levels.Methods Forty eight patients with coronary heart disease were assigned to atorvastatin only group(20 mg/d of atorvastatin,n=22) or combined therapeutic group(20 mg/d of atorvastatin and 1.0 g/d of probucol,n=26) in a randomized manner.Serum levels of ox-LDL and ox-LDL-Ab were detected before and after treatment.Results After treated with atorvastatin only and combined therapy the levels of serum LDL,ox-LDL,TC and TG were significantly decreased(P<0.01),and those in combined therapy decreased even more markedly(P<0.05).Alone in the treatment group ox-LDL antibodies had no significant effect(P>0.05).Combined treatment group can significantly reduce the level of ox-LDL antibody(P<0.01).Conclusions Both atorvastatin alone and atorvastatin combined probucol can decrease the levels of ox-LDL in patients with coronary heart disease,and those in combined therapy decreased even more markedly.Alone in the treatment group ox-LDL antibodies had no significant effect.But combined treatment group can significantly reduce the level of ox-LDL antibody levels.