Probucol治疗高脂血症的近期临床疗效观察

为观察Probucol的调脂、抗动脉粥样肝硬化作用,将60例原发性高指血症患者随机分为:probucol(0.5,日二次)治疗组和Simvatatin(5mg,睡前一次)对照组各30例,治疗4周,结果:降低TC分别为18.58％、21.98％,各组内P<0.001,组间P>0.05;降低TC-HDL-C/HDL-C比值:10.98％、35.61％,组内P<0.02,P<0.001,组间P<0.001。总有效率TC:83.33％,86.67％,组间P>0.05;TC-HDL-C/HDL-C:56.67％,93.33％,组间P<0.005。其他各生化指标无显著变化.副反应尽微。结论:Probucol调脂抗动脉粥样硬化作用迅速、可靠、无明显不良反应,值得临床广泛应用。

Probucol对碱性成纤维细胞生长因子和过氧化氢促大鼠血管平滑肌细胞增殖的影响

目的 :研究probucol对bFGF和H2 O2 促大鼠血管平滑肌细胞 (VSMC)增殖的影响。方法 :采用MTT、细胞计数和 [3H]-TdR掺入法观察probucol对bFGF和H2 O2 促VSMC增殖的影响。结果 :①Probucol抑制bFGF和H2 O2 刺激VSMC增殖和DNA合成 ,且呈剂量依赖性。Probucol+bFGF和probucol+H2 O2 组与bFGF和H2 O2 组比较 ,细胞计数、A值和 [3H]-TdR掺入量分别下降了 40 0 %、39 1%、45 5 %和 46 9%、45 0 %、39 5 % (P <0 0 5 ,P <0 0 1)。②bFGF和H2 O2 刺激前给予probucol预处理 2 4h能显著抑制VSMC增殖和DNA合成 (P <0 0 5 ) ,而bFGF和H2 O2 刺激后 2 4h给予probucol则无明显影响 (P >0 0 5 )。结论 :Probucol能显著抑制bFGF和H2 O2 刺激的VSMC增殖和DNA合成 ,但对bFGF和H2 O2 预刺激诱导的细胞增殖无抑制作用。

8羟基脱氧鸟苷在2型糖尿病大鼠肾脏的表达及Probucol的影响

目的:观察8-羟基脱氧鸟苷(8-hydroxy-deoxyguanosine,8-OHdG)在2型糖尿病(Diabetesmellitus,DM)模型大鼠肾脏的表达及普罗布考(Probucol)对它的影响。方法:将大鼠分为正常对照组(Normol rats,C)、DM组(Diabetic rats,D)、普罗布考治疗组(Diabetic rats treated with probucol,N),比较各组大鼠肾组织中丙二醛(Malondialdehyde,MDA)含量、超氧化物岐化酶(Superoxide dismutase,SOD)活性,和8羟基脱氧鸟苷(8-OHdG)含量,同时观察血糖、血胰岛素、肾功能和肾脏形态变化。结果:与正常组比较,DM组血液中MDA含量明显上升(P<0.05),SOD活性显著下降(P<0.05),8-OHdG增多(P<0.05),肾功能和肾脏形态受损,而普罗布考治疗组的上述表达较DM组明显改善。结论:8-OHdG在DM肾病(Diabeticnephropathy,DN)中的表达明显增加,而普罗布考可以通过抑制氧化应激反应对2型DM模型大鼠肾脏产生保护作用。

Improved dissolution and oral absorption by co-grinding active drug probucol and ternary stabilizers mixtures with planetary beads-milling method

The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(>60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.

A randomized, open-label, multicentre study to evaluate plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus and arteriosclerosis obliterans when treated with Probucol and Cilostazol

Objectives To evaluate the plasma atherosclerotic biomarkers in patients with type 2 diabetes mellitus （T2DM） and arteriosclerosis obliteran （ASO） when treated with Probucol plus Cilostazol in combination and individually. Methods In this open-label study, patients aged 40-75 years were randomized to receive conventional therapy alone, or with Cilostazol 100 mg bid, or with Probucol 250 mg bid, or with both in combination. Endpoints included changes in plasma biomarker and safety at 12 weeks. Results Of the 200 randomized pati- ents, 165 for per-protocol and 160 for the safety （QTc intervals） were set, respectively. Probucol significantly reduced total cholesterol （P 〈 0.001）, low-density lipoprotein cholesterol （LDL-C）, （P = 0.01）, and high-density lipoprotein cholesterol （HDL-C） （P 〈 0.001） compared with conventional therapy. Cilostazol was effective in increasing HDL-C （P = 0.002） and reducing triglycerides levels （P 〈 0.01） compared with conventional therapy. A trend towards significance was observed for the difference between conventional therapy alone and Probucol plus Cilostazol group for the change in oxidized low-density lipoprotein （Ox-LDL, P = 0.065）. No significant effects on the majority of the remaining biomarkers were found across the treatment groups. Conclusions We have confirmed that Ox-LDL could be a possible plasma atherosclerotic biomarker among the evaluated biomarkers, which reflected the synergetic effect of Cilostazol plus Probucol in patients with T2DM and ASO shown previously in preclinical studies.

Probucol抑制氧化低密度脂蛋白诱导的大鼠主动脉平滑肌细胞增殖

目的:研究Probucol抑制ox-LDL诱导RASMCs增殖与信号蛋白分子ERK1/2、MKP-1、HO-1和Trx-1表达之间的关系。方法:采用MTT、流式细胞术和Western blotting观察ox-LDL刺激条件下probucol对细胞周期、细胞增殖和凋亡、ERK1/2、MKP-1、HO-1和Trx-1表达的影响。结果:(1)Probucol抑制ox-LDL刺激RASMCs增殖:100μmol/Lprobucol+35mg/Lox-LDL组与35mg/Lox-LDL组比较,A值下降了34.9%(P<0.01);(2)Probucol通过使RASMCs停滞在G0/G1期和诱导细胞凋亡2种方式抑制ox-LDL刺激细胞增殖。(3)ox-LDL显著抑制MKP-1的蛋白表达,与对照组比较下降了60.0%(P<0.01),同时使p-ERK1/2表达增加了34.7%;Probucol使MKP-1蛋白表达显著增加2倍,p-ERK1/2表达降低了15.7%(P<0.01);(4)35mg/Lox-LDL使细胞内Trx-1蛋白表达下降28.9%(P<0.05),HO-1蛋白表达轻度增加(P<0.05)。与ox-LDL组比较,probucol使Trx-1蛋白表达增加了91.6%(P<0.01),HO-1表达增加31.9%(P<0.01)。结论:Probucol通过增强MKP-1和HO-1蛋白表达、抑制细胞周期运转和诱导细胞凋亡的机制抑制RASMCs增殖。

Effect of probucol on insulin resistance in patients with non-diabetic chronic kidney disease

Background Insulin resistance （IR） is present at all stages of chronic kidney disease （CKD） and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus （DM） patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group （0.5 g, twice daily） or the control group using a 1： 1 treatment ratio. IR was determined using a homeostatic model assessment-IR （HOMA-IR） index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate （eGFR）, body mass index （BMI）, cholesterol, triglycerides, high-density lipoprotein （HDL）, low-density lipoprotein （LDL）, and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased （P 〈 0.001） compared to the value before treatment （average decrease： 1.45; range： -2.90 to -0.43）. The HOMA-IR index in the control group increased （average increase： 0.54; range： -0.38 to 1.87）. For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR （P = 0.041）, cholesterol （P = 0.001）, fasting insulin （P 〈 0.001）, and fasting C-peptide （P = 0.001）. Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.

Protective effects of probucol in rats with postoperative acute renal failure

Objective We investigated the protective effect of probucol in rats with acute renal failure caused by various ischemia-reperfusion injuries(IRIs) after surgery.Methods Forty male Sprague-Dawley rats were randomly divided into a sham operation group(S group), ischemia reperfusion group(IR group), probucol low-dose treatment group(probucol + IR group 1, P+ IR1 group; probucol 250 mg/kg intragastric administration daily), and probucol high-dose treatment group(P + IR2 group; probucol 500 mg/kg intragastric administration daily). Rats in the S and IR groups were intragastrically administered with warm water every day. After 1 week, the kidney IRI rat models were prepared, after which the rats were fed for another week, and blood, urine, and the kidney tissue specimens were retained. A series of biochemical indices, superoxide dismutase(SOD), and malondialdehyde in the serum and kidney tissues were detected, and pathological changes in renal tissue were observed.Results Twenty-four-hour urinary protein excretion, urinary NAGase, Cys C, blood urea nitrogen(BUN), and creatinine were significantly lower in the P + IR1 and P + IR2 groups than in the IR group(P < 0.05). Superoxide dismutase in the serum and renal tissue increased significantly, malondialdehyde decreased significantly(P < 0.05), renal pathological injury was alleviated, and the kidney index improved significantly(P < 0.05).Conclusion Probucol can relieve various types of acute renal failure in postoperative rats.

Both Atorvastatin and Probucol Can Down-regulate BMP-2 Expression Induced by Oxidized Low Density Lipoprotein in Human Umbilical Vein Cells

Objectives Bone morphogenetic protein-2 (BMP-2) plays an key role both in vascular development and pathophysiological processes. However, the mechanisms of oxidized low density lipoprotein (ox-LDL) and combinated with atorvastatin or probucol on BMP-2 expression are entirely unknown in human umbilical vein cells. Methods The HUVECs were treated by ox-LDL and combinated with atorvastatin, probucol. The expression of BMP-2, NF-κB65, PPARγ mRNA was examined by RT-PCR analysis and ELISA method. The MDA and SOD were detected by routine methods. Results Ox-LDL can induced BMP-2 mNRA expression, associated with NF-κB65 mNRA expression activation. Both atorvastatin and probucol can suppress BMP-2 and NF-κB65 expression induced by oxLDL and upregulate the expression of PPARγ. Furthermore, the increase of supernatant MDA levels and decrease of supernatant SOD levels resulted from oxLDL treatment can be reversed by probucol or atorvastatin. Conclusions OxLDL-induced BMP-2 mNRA expression can be suppressed by atorvastatin and probucol, which may be accomplished by activating NF-κB65 expression and upregulating the expression of PPARγ. Our findings also indicate that that BMP-2 mNRA expression includes the activation of reactive oxygen species.

Influence of probucol-assisted retinal photocoagulation therapy on the visual performance and serum biochemical indexes in patients with early proliferative diabetic retinopathy

Objective: To explore the influence of probucol-assisted retinal photocoagulation therapy on the visual performance and serum biochemical indexes in patients with early proliferative diabetic retinopathy. Methods: A total of 170 patients with early proliferative DR who were treated in the hospital between December 2014 and May 2017 were retrospectively analyzed and divided into the control group (n=107) who received retinal photocoagulation therapy alone and the probucol group (n=63) who received probucol-assisted retinal photocoagulation therapy. The differences in the contents of visual performance indexes as well as serum angiogenesis indexes, inflammatory mediators and oxidative stress indexes were compared between the two groups before treatment and after 6 weeks of treatment. Results: Before treatment, the differences in the levels of visual performance indexes as well as serum contents of angiogenesis indexes, inflammatory mediators and oxidative stress indexes were not statistically significant between the two groups of patients. After 6 weeks of treatment, mean vision, 30 visual acuity and 30-60 visual acuity of probucol group were higher than those of control group;serum angiogenesis indexes HIF-1, VEGF and Ang-2 contents were lower than those of control group;serum inflammatory mediators ICAM-1, IL-2, IL-23 and TNF-α contents were lower than those of control group;serum oxidative stress index MDA content was lower than that of control group whereas TAC content was higher than that of control group. Conclusion: Probucol-assisted retinal photocoagulation therapy can effectively optimize the visual performance and promote the homeostasis recovery in patients with early proliferative diabetic retinopathy.

普罗布考联合阿托伐他汀治疗多发脑血管狭窄合并主动脉弓溃疡斑块病例报道

预防卒中的发生和复发是缺血性脑血管病防治的首要任务,多发脑血管狭窄合并主动脉弓溃疡斑块的患者缺血性卒中复发的风险显著升高。本文介绍1例普罗布考联合阿托伐他汀治疗多发脑血管狭窄合并主动脉弓溃疡斑块患者的发病和治疗情况。该例患者表现为轻度神经功能缺损,住院期间发现多发脑血管狭窄合并主动脉弓溃疡斑块,在序贯双联抗血小板治疗3个月后持续阿司匹林单药抗血小板治疗,并全程联合普罗布考和阿托伐他汀强化降脂、抗氧化治疗,随访25个月,无卒中复发,且各项影像学和血液学检查指标保持稳定。

普罗布考联合阿托伐他汀钙治疗急性脑梗死的疗效

目的评估普罗布考与阿托伐他汀钙联合治疗急性脑梗死(acute cerebral infarction,ACI)的疗效,以提供ACI的治疗参考方案。方法回顾性收集2018年1月—2023年9月在重庆市急救医疗中心就诊,发病24 h内住院的ACI患者资料。纳入患者需满足:接受了阿托伐他汀钙(20 mg,每晚1次)单药或联用普罗布考(0.5 mg,每日2次)调节血脂治疗,且治疗周期为3个月以上。根据是否联用普罗布考分为联合治疗组和对照组,比较两组治疗后神经功能(使用NIHSS评估)、神经功能结局(使用mRS评估)、生活能力(使用Barthel指数评估)以及血脂水平的差异。结果研究共入组102例患者,其中联合治疗组56例,对照组46例。两组的基线资料差异无统计学意义。治疗后14 d两组的NIHSS评分和血脂水平、治疗3个月后的血脂水平均较本组治疗前显著改善(均P<0.001)。治疗14 d时,联合治疗组的NIHSS评分(P=0.031)、TC(P=0.005)和LDL-C(P=0.044)水平低于对照组,Barthel指数(P=0.004)高于对照组,差异有统计学意义。治疗3个月时,联合治疗组的mRS评分(P<0.001)、TC(P<0.001)、TG(P=0.002)和LDL-C(P<0.001)水平低于对照组,Barthel指数高于对照组(P<0.001),差异有统计学意义。随访3个月期间联合治疗组的脑梗死复发率为0,对照组为2.17%,但差异无统计学意义(P=0.268)。结论普罗布考联合阿托伐他汀钙治疗ACI急性期患者,相较于单独使用阿托伐他汀钙,具有更佳的临床疗效,能有效降低血脂水平并改善患者的神经功能及生活能力。

普罗布考联合瑞舒伐他汀对缺血性脑卒中患者内皮细胞功能及血清铁调素25水平的影响

目的:探讨普罗布考联合瑞舒伐他汀对缺血性脑卒中(IS)患者内皮细胞功能和血清铁调素25(Hepc25)水平的影响。方法:选取2020年5月~2023年4月期间于某院就诊的130例IS患者作为研究对象,采用随机数字表法分为对照组和观察组,每组65例。根据患者病情给予调整血压、降低体温、维持呼吸、控糖、溶栓、抗凝血、抗血小板、神经保护、降低颅内压等常规治疗,对照组患者在常规治疗基础上加用瑞舒伐他汀钙片,观察组患者在对照组治疗基础上加用普罗布考片,两组均持续治疗6个月。比较两组患者临床疗效、神经功能[美国国立卫生研究院卒中量表(NIHSS)、Barthel指数(BI)和蒙特利尔认知评估量表(MoCA)]、内皮细胞功能[血管内皮生长因子(VEGF)、基质细胞衍生因子-1α(SDF-1α)、血管生成素(Ang)和血小板衍生生长因子(PDGF)]、血清Hepc25水平及不良反应发生情况。结果:治疗后,观察组患者治疗总有效率(93.85%)高于对照组(73.85%,P<0.05);两组患者NIHSS评分和血清Hepc25水平均降低,且观察组低于对照组(P<0.05);BI、MoCA评分和VEGF、SDF-1α、Ang、PDGF水平均升高,且观察组高于对照组(P<0.05)。治疗期间,两组患者不良反应总发生率比较无统计学差异(P>0.05)。结论:在常规治疗基础上,普罗布考联合瑞舒伐他汀治疗IS患者临床疗效较佳,可有效改善IS患者病情,提高内皮细胞功能,降低血清Hepc25水平,且未增加不良反应的发生风险。

麝香保心丸联合普罗布考对老年冠心病合并糖尿病患者血脂代谢及血管内皮功能的影响

目的分析麝香保心丸联合普罗布考对老年冠心病合并糖尿病患者血脂代谢及血管内皮功能的影响。方法前瞻性选取北京市朝阳区双桥医院2021年1月至2022年10月收治的老年冠心病合并糖尿病患者102例,按照随机数字表法分为观察组与对照组,每组各51例,对照组采用常规疗法+普罗布考治疗,观察组在对照组基础上采用麝香保心丸治疗。治疗3个月后,统计分析两组临床疗效、血脂代谢指标[总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白(Apo)A1和ApoB]、血管内皮功能指标(内皮素-1、血栓素B2、一氧化氮)、心功能指标[左室收缩末内径(LVESD)、左室舒张末内径(LVEDD)、左室射血分数(LVEF)和左室质量指数(LVMI)]、血糖指标[空腹血糖(FBG)、糖化血红蛋白(GHb)及餐后2 h血糖(2 h PBG)]水平。结果观察组临床总有效率为94.12%,高于对照组(78.43%),差异有统计学意义(P<0.05)。治疗3个月后,观察组的总胆固醇、甘油三酯、LDL-C及ApoB水平分别为(5.15±0.88)mmol/L、(1.71±0.23)mmol/L、(3.33±0.71)mmol/L、(0.81±0.17)g/L,均低于对照组[(5.86±0.91)mmol/L、(2.13±0.26)mmol/L、(3.97±0.85)mmol/L、(1.08±0.18)g/L],HDL-C和ApoA1水平分别为(1.18±0.25)mmol/L、(1.44±0.25)g/L,均高于对照组[(0.96±0.22)mmol/L、(1.21±0.22)g/L],差异均有统计学意义(P<0.05)。治疗3个月后,观察组的内皮素-1及血栓素B2水平分别为(58.31±4.13)、(163.11±10.06)ng/L,均低于对照组[(62.11±4.41)、(179.31±11.11)ng/L],一氧化氮水平为(71.22±6.55)μmol/L,高于对照组[(67.58±5.61)μmol/L],差异均有统计学意义(P<0.05)。治疗3个月后,观察组的LVESD及LVMI分别为(35.13±2.23)mm、(109.85±11.29)g/m^(2),均低于对照组[(38.42±2.47)mm、(121.31±12.84)g/m^(2)],LVEDD、LVEF分别为(55.84±4.36)mm、(60.05±6.14)%,均高于对照组[(51.21±4.43)mm、(55.25±5.38)%],差异均有统计学意义(P<0.05)。治疗3个月后,观察组的FBG、GHb及2 h PBG水平分别为(6.41±1.01)mmol/L、(5.37±0.74)%、(8.20±1.34)mmol/L,均低于对照组[(7.31±1.04)mmol/L、(6.12±0.57)%、(9.68±1.22)mmol/L],差异均有统计学意义(P<0.05)。结论麝香保心丸联合普罗布考可有效改善老年冠心病合并糖尿病患者血脂代谢、血管内皮功能、心功能、血糖水平,临床综合疗效显著,值得临床予以推广应用。

依达拉奉配合普罗布考治疗缺血性脑卒中的效果及对患者近期预后的影响

目的探讨依达拉奉配合普罗布考治疗缺血性脑卒中(IS)的效果及对患者近期预后的影响。方法将2022年11月至2023年10月我院收治的110例IS患者,按照入组顺序分为两组。对照组采用依达拉奉治疗,观察组采用依达拉奉配合普罗布考治疗。比较两组治疗效果、血清指标及预后。结果观察组治疗总有效率高于对照组(P<0.05)。治疗后,观察组SOD高于对照组,NSE、hs-CRP低于对照组(P<0.05)。观察组短期预后良好率高于对照组(P<0.05)。结论依达拉奉联合普罗布考治疗IS的效果较好,可改善患者的短期预后,其机制可能与调节SOD、NSE、hs-CRP的表达有关。

Effect of probucol on vascular remodeling due to atherosclerosis in rabbits： an intravascular ultrasound study

Background Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis. Methods Aortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks＇ atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% （wt/wt） probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed. Results Probucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group （56% vs. 21%, 18% vs. 54%, respectively, both P〈0.01）. In addition, the probucol group showed a smaller mean remodeling index relative to the control group （0.93 ± 0.13 vs. 1.05 ± 0.16, P 〈0.01）. Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S （all P 〈0.01）. Conclusions These findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques.

普罗布考联合依达拉奉右莰醇对缺血性脑卒中患者血流动力学及神经功能的影响

目的探究普罗布考联合依达拉奉右莰醇对缺血性脑卒中(cerebral ischemic stroke,CIS)患者的疗效,及其对脑血流动力学和神经功能的影响。方法回顾性选取82例CIS患者为研究对象,依据不同治疗方案将其分为对照组、观察组,各41例。对照组给予依达拉奉右莰醇,观察组给予依达拉奉右莰醇+普罗布考,均连续治疗14 d。比较两组的临床疗效,美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分,改良Barthel评分(modified Barthel index,mBI),简易精神状态检查表(mini-mental state examination,MMSE)评分,大脑中动脉平均流速、峰流速对称性差值(difference in symmetry of peak flow velocity,DVp)、平均流速对称性差值(difference in symmetry of average flow velocity,DVm)、峰流速,血清闭合蛋白、高敏C反应蛋白(hs-CRP)、基质金属蛋白酶(matrix metalloproteinase,MMP)-9、网膜素-1及不良反应的发生情况。结果治疗后观察组总有效率高于对照组(92.68%vs.75.61%,P<0.05)。治疗后观察组mBI、MMSE评分高于对照组,NIHSS评分低于对照组(P<0.01),而大脑中动脉平均流速、峰流速及网膜素-1水平均高于对照组,DVp、DVm及血清闭合蛋白、hs-CRP、MMP-9水平均低于对照组(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论普罗布考联合依达拉奉右莰醇对CIS疗效确切,可改善患者脑血流动力学,抑制炎症反应,减轻神经功能障碍,且安全性较高。

普罗布考联合他汀类药物治疗颈动脉斑块的meta分析

目的探究普罗布考联合他汀类药物治疗颈动脉斑块的疗效。方法以“普罗布考”“他汀”“颈动脉”为中文关键词,检索中文数据库中国知网、维普网、万方数据库,以“carotid artery”“probucol”“statins”为英文关键词,检索英文数据库PubMed、Cochrane Library、Embase,筛选普罗布考联合他汀类药物治疗颈动脉斑块的随机对照试验。检索时间为数据库建立至2023年12月17日。以单用他汀类药物治疗为对照组,他汀类药物联合普罗布考治疗为联合治疗组。参照Cochrane偏倚风险评估对纳入的研究进行质量评价。主要结局指标包括颈动脉内-中膜厚度(intima-media thickness,IMT),次要结局指标包括TC水平、hs-CRP水平、卒中事件发生等。采用RevMan 5.1软件进行meta分析。结果最终纳入11项随机对照试验,共纳入3251例患者。meta分析显示,在降低I MT方面,联合治疗组优于对照组[标准化均数差(standardized mean difference,SMD)-0.93,95%CI-1.66~-0.20,P<0.001];在降低TC水平方面,联合治疗组优于对照组(SMD-1.08,95%CI-1.60~-0.55,P<0.001);在降低hs-CRP水平方面,两组差异无统计学意义(SMD-1.22,95%CI-2.48~0.04,P=0.060);在减少卒中事件发生方面,联合治疗组优于对照组(RR 0.34,95%CI 0.17~0.65,P=0.001)。结论普罗布考联合他汀类药物治疗颈动脉斑块疗效更优,可降低患者的TC水平,并减少卒中事件发生。

Effect of probucol on autophagy and apoptosis in the penile tissue of streptozotocin-induced diabetic rats

Autophagy and apoptosis have been regarded as important processes in the development of diabetic erectile dysfunction(DMED).Probucol is considered to have anti-apoptotic effects,but its relationship with autophagy has not been reported.The aim of this study was to investigate the effects and mechanisms of probucol on erectile function.Thirty Sprague–Dawley(SD)male rats(12 weeks old)were fasted for 12 h.Twenty SD rats were injected with a single intraperitoneal injection of 60 mg kg−1 streptozotocin(STZ).Ten rats were given vehicle only and used as a sham group.After 72 h,20 STZ-treated rats with random blood glucose concentrations consistently greater than 16.7 mmol l^−1 were used as successfully established diabetic rats.The diabetic rats were divided randomly into two groups and treated with a daily gavage of probucol at a dose of 0 or 500 mg kg^−1 for 12 weeks.After treatment,the intracavernous pressure(ICP)was used to measure erectile function upon electrical stimulation of the cavernous nerve.After euthanasia,penile tissue was examined using immunohistochemistry and Western blot to assess the protein levels of B-cell lymphoma-2(Bcl-2),BCL2-associated X(Bax),microtubule-associated protein light chain 3-II(LC3-II),mammalian target of rapamycin(mTOR),and sequestosome 1(P62).Caspase-3 activity was measured to determine apoptosis using a caspase-3 assay kit.After 12 weeks of treatment,the erectile function of the probucol group was significantly better than that of the DM group(P<0.05).Bax and LC3-II protein expression and caspase-3 activity were significantly lower in the probucol group than those in the DM group(all P<0.05),while Bcl-2,mTOR,and P62 protein expression levels were significantly higher than those in the DM group(all P<0.05).We demonstrated that probucol inhibited apoptosis and autophagy in STZ-induced diabetic rats.

阿加曲班联合普罗布考治疗进展性卒中患者效果及对炎症因子、促动脉硬化指数的影响

目的 探讨阿加曲班联合普罗布考治疗进展性卒中的临床疗效,并分析其对炎症因子、促动脉硬化指数(AIP)、血小板功能的影响。方法 回顾性选取2019年10月至2022年10月进展性卒中患者80例,依据治疗方案不同分为单一组40例(普罗布考治疗)、联合组40例(阿加曲班联合普罗布考治疗)。比较两组临床疗效、安全性及治疗前后美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数评定量表(BI)评分、促动脉硬化指数(AIP)、神经功能[B型利钠肽(BNP)、神经元特异性烯醇化酶(NSE)、β淀粉样蛋白-1-42(Aβ1-42)]、炎症因子[白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1(MCP-1)、脂蛋白相关磷脂酶A2(Lp-PLA2)]、血小板功能。结果 联合组临床疗效优于单一组(P<0.05);不良反应对比无明显差异(P>0.05);与单一组比较,联合组治疗后NIHSS评分、AIP降低,BI评分升高(P<0.05);与单一组比较,联合组治疗后血清BNP、NSE、Aβ1-42、IL-1β、MCP-1、Lp-PLA2水平降低(P<0.05);与单一组比较,联合组治疗后血小板聚集率、血小板体积降低(P<0.05)。结论 阿加曲班联合普罗布考治疗进展性卒中的疗效确切,可改善神经功能、动脉粥样硬化,提高日常生活能力,减轻炎症反应程度,抑制血小板活化,且具有一定安全性。