fenofibrate在缺血再灌注中的作用研究

fenofibrate是降脂药fibrate家族中的一种药物,目前主要临床应用是降低血胆固醇水平[1]。作为PPAR-α的激动剂,fenofibrate以转录因子的角色参与基因表达,调节细胞内糖类和脂肪代谢以及脂肪组织分化[2]。最近研究发现,除了降低血脂以外,fenofibrate还通过抗氧化应激和抗炎,在缺血再灌注模型中发挥减轻损伤的作用。本文就fenofibrate在抗氧化抗炎和缺血再灌注中的研究做一综述。

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is a common health problem with a high mortality burden due to its liver- and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus(T2DM) and metabolic syndrome(MetS).Impaired hepatic fatty acid(FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors(PPARs)are involved in lipid and glucose metabolic pathways.The novel concept is that the activation of the PPARαsubunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis.These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet,T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent.In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

Fenofibrate Pre-treatment Suppressed Inflammation by Activating Phosphoinositide 3 Kinase/Protein Kinase B(PI3K/Akt) Signaling in Renal Ischemia-Reperfusion Injury

The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury（IRI） in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups： sham-operated group（sham）, IRI＋saline group（IRI group）, IRI＋Fenofibrate（FEN） group. Normal saline or Fenofibrate（3 mg/kg） was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8（IL-8）, tumor necrosis factor alpha（TNF-α） and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B（PI3K/Akt） signaling and peroxisome proliferator-activated receptor-α（PPAR-α） were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.

Inhibitory Effects of Fenofibrate on Plasminogen Activator Inhibitor-1 Expression in Human Endothelial Cells

The effects of fenofibrate on plasminogen activator inhibitor-1 （PAI-1） expression in human umbilical endothelial cell-derived transformed cell line--ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate （0, 10, 50, 100 μmol/L） for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction （RT-PCR） and Western blot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate （10 pmol/L）, the expression levels of PAI-1 mRNA and protein were 0. 65±0.05 and 0.96± 0. 11 respectively, significantly lower than in the control group （0.78±0.03 and 1.21±0.15, respectively, P〈0.05）. PAI-1 antigenic contents （24.52±8.39） in ECV304 cells treated with 10 μmol/L fenofibrate were significantly lower than those in the control group （6.98±5.12, P〈0.05）. It was concluded that fenofibrate inhibited the expression of PAF1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.

Preparation and pharmacokinetic study of fenofibrate cubic liquid crystalline

An LCC delivery system for Fenofibrate (Fen) was developed to improve its poorly oral bioavailability. Fen-LCC preparation methods were screened, and the prepared Fen-LCC was then characterized by a polarizing microscope and transmission electron microscopy (TEM).The spray drying technique was selected to dry and solidify particles into powder. The in vitro release of Fen-LCC was measured and in vivo pharmacokinetic experiments were carried out on rats after oral administration. Particles prepared through the high-temperature input method exhibited structural characteristics of LCC, and re-dissolved particles maintained the same features. The LCC delivery system can significantly improve in vitro release outcomes. After oral administration, AUCs of the suspension and LCC systems were measured at 131.6853 μg·h/ml and 1435.72893 μg·h/ml, respectively. The spray drying process presented here better maintains cubic structures, and the LCC system significantly improves bioavailability levels.

Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy

Fenofibrate is mainly used to reduce cholesterol level in patients at risk of cardiovascular disease. Thermal transition study with the help of differential scanning calorimetry （DSC） shows that the aforesaid active pharmaceutical ingredient （API） is a good glass former. Based on our DSC study, the molecular dynamics of this API has been carried out by broadband dielectric spectroscopy （BDS） covering wide temperature and frequency ranges. Dielectric measurements of amorphous fenofibrate were per- formed after its vitrification by fast cooling from a few degrees above the melting point （Tm=354.11 K） to deep glassy state. The sample does not show any crystallization tendency during cooling and reaches the glassy state. The temperature dependence of the structural relaxation has been fitted by single Vogel- Fulcher-Tamman （VFT） equation. From VFT fit, glass transition temperature （Tg） was estimated as 250.56 K and fragility （m） was determined as 94.02. This drug is classified as a fragile glass former. Deviations of experimental data from Kohlrausch-Williams-Watts （KWW） fits on high-frequency flank of α-peak indicate the presence of an excess wing in fenofibrate. Based on Ngai＇s coupling model, we identified the excess wing as true Johari-Goldstein （JG） process. Below the glass transition temperature one can clearly see a secondary relaxation （γ） with an activation energy of 32.67 kJ/mol.

Biopsy-confirmed fenofibrate-induced severe jaundice:A case report

BACKGROUND Drug-induced liver injury(DILI)is the leading cause of acute liver failure in the United States.DILI is mainly caused by painkillers and fever reducers,and it is often characterized by the type of hepatic injury(hepatocellular or cholestatic).This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease.We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases.CASE SUMMARY A 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test.Abdominal ultrasound and computed tomography showed no biliary obstruction or nonspecific findings in the liver.Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis.Following the biopsy,steroid therapy was initiated and after 3 wk of treatment,the total bilirubin level was reduced to 7.22 mg/dL.CONCLUSION In patients with hyperlipidemia,treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis,warranting clinical attention.

Dissolution improvement of fenofibrate by melting inclusion in mesoporous silica

In this study,using mesoporous silica for the solubility enhancement of poorly watersoluble drug was investigated.Although the incorporating drug into mesoporous silica is generally performed through the solvent method,the new melting method was proposed in the present study.Fenofibrate,a poorly water-soluble drug,was incorporated into mesoporous silica by solvent method and melting method.The obtained samples were observed by SEM and their physicochemical properties were evaluated by PXRD and DSC measurement.The dissolution and supersaturated property were also investigated.The results from SEM,PXRD and DSC measurement showed that drug could be loaded into pore via the melting method as well as by the solvent method.The drug loaded quantity depended on the pore volume.Drug up to 33%could be incorporated into mesoporous silica and existed in amorphous state.When drug was overloaded or difficulty in incorporation into pore was found,recrystallization of drug occurred at the outer surface of mesoporous silica.From the dissolution test,samples prepared by solvent method and melting method gave the supersaturated drug concentration which sample from melting method showed superior dissolution to the one from solvent method.From this study,drug was efficiently incorporated into mesoporous silica by the melting method which is a simple and solvent-free process,and the aqueous solubility enhancement of poorly watersoluble drug was achieved.

Fenofibrate for the prevention of progression of non-proliferative diabetic retinopathy:review,consensus recommendations and guidance for clinical practice

The prevalence of diabetic retinopathy(DR),and associated morbidity is high in the Asia-Pacific region.Emerging evidence suggests a potential role for fenofibrate in the prevention of progression of DR,especially in patients with cardiovascular risk,and pre-existing mild-to-moderate DR.Fenofibrate has also been found to reduce maculopathy,and the need for laser treatment in these patients.Considering these benefits of fenofibrate,a group of experts from the fields of endocrinology and ophthalmology convened in May 2017,to discuss on the the mechanism of action,and clinical efficacy of fenofibrate in DR.The findings from key clinical studies on fenofibrate in DR were reviewed by the experts,and consensus statements were derived to define the role of fenofibrate in the prevention and treatment of DR.The statements were rated based on the GRADE criteria.An algorithm was also developed for the screening and treatment of DR in patients with type 2 diabetes(T2D),and the place of fenofibrate was defined in the algorithm.The expert recommendations,and the algorithm provided in this review will serve as a guide to the clinicians to reconsider the adjunctive use of fenofibrate for preventing the progression of DR in selected T2D patients.

Clinical research of fenofibrate and spironolactone for acute central serous chorioretinopathy

AIM：To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy（CSCR）.METHODS： Totally 60 patients（60 eyes） with a history of acute CSCR were randomed into two groups： group A with combination of fenofibrate（200 mg） and spironolactone（100 mg）,and group B with only fenofibrate（200 mg）.They were taken half an hour before meals and once per day for 8wk.The changes of the visual acuity,subjective symptom,ocular surface disease index（OSDI）,the tear film and optical coherence tomography were observed at 2,4,6,and 8wk before and after treatment.RESULTS： The best corrected visual acuity（BCVA,log MAR） was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B（P 〈0.05）,respectively.After 8wk treatment,the central subfield thickness（CST）,and subretinal fluid volumn（SFV） decreased significantly to 49.5% and 78.8% in group A,37.0% and 57.2% in group B.There were significant differences of CST and SFV in both groups（all P 〈0.05）.CONCLUSION：Fenofibratecombinedwithspironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only.

Prolonged cholestasis after raloxifene and fenofibrate interaction: A case report

Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis.

Spray drying of fenofibrate loaded nanostructured lipid carriers

The conversion of aqueous dispersion of nanostructured lipid carriers(NLCs) into dry powder by spray drying could be a useful approach to render NLCs with better physical chemical stability than the aqueous dispersion. In this study, aqueous NLC dispersion containing fenofibrate was converted into dry, easily reconstitutable powder using spray drying. A central composite face centered design(CCFD) was used to investigate the influence of the ratio of lipid to protectant(mannitol and trehalose) and crystallinity of spray-dried powder on the particle size, yield and residual moisture content of the dried powder. A linear relationship(R2= 0.9915) was established between the crystalline content of the spray-dried powders against the ratio of mannitol to trehalose from 3:7 to 10:0(w/w). Spray drying of NLC aqueous dispersion using a mannitol and trehalose mixture resulted in an increase in particle size of the NLCs after reconstitution in water as compared to that in the initial aqueous dispersion. The decrease in crystallinity of the dry powder by reducing the ratio of mannitol to trehalose could improve the reconstitution of the NLCs in water. However the yield and residual moisture content of dry powder decreased with an increase in the ratio of mannitol to trehalose. Lipid nanoparticles were able to retain the drug incorporation and the prolonged drug release profile after spray drying. The experimental model was robust, and suggested that spray drying is a viable technique for the conversion of NLCs into dry powder.

Determination of Fenofibrate and the Degradation Product Using Simultaneous UV-Derivative Spectrometric Method and HPLC

Two new selective, precise, and accurate methods were developed for the determination of fenofibrate in the presence of its basic degradation product. In the first method fenofibrate was determined using an algorithm bivariate calibration derivative method, in which an optimum pair of wavelengths was chosen for the determination of different binary mixtures. In the second method (HPLC), separation was achieved on RESTEK Pinnacle II phenyl column (5 μm, 250 × 4.6 mm) and Pinnacle II phenyl (5 μm, 10 × 4 mm) guard cartridge using a mobile phase consisting of methanol –0.1% phosphoric acid (60:40, v/v) at a flow rate 2 mL●min–1, and the column oven temperature was set at 50°C. The UV detector was time programmed at 302 nm and 289 nm for the internal standard (I.S.) and fenofibrate, respectively. The proposed methods were successfully applied for the determination of fenofibrate and its degradation product in the laboratory-prepared mixture and in pharmaceutical formulation. The assay results obtained using the bivariate method were statistically compared to those of the HPLC method and good agreement was observed.

Formulation and Characterization of Fenofibrate Loaded Solid Dispersion with Enhanced Dissolution Profile

Fenofibrate (FF) is an anti-hyperlipidaemic drug belonging to BCS class-II (low solubility, high permeability). Its bioavailability is limited by the dissolution rate. This study was aimed to enhance the rate of dissolution of poorly water soluble drug, FF. Initially, solid dispersions of fenofibrate (SDFs) were formulated with Carplex-80 or PEG-4000 or in combination at various weight ratios and were subjected to dissolution study. On the basis of drug release at various time intervals, the formulation producing maximum drug concentration was evaluated physicochemically using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). It was observed that the peak drug concentration was obtained at 120 min of dissolution by formulation SDF-7, which contains a mixture of Carplex-80 and PEG-4000 at weight ratio 1:5:6 of FF:PEG-4000:Carplex-80, respectively. Thus, the extent of drug release by SDF-7 was maximized by 2.5-fold than that of pure FF. Physicochemical characterization revealed the reason for this increased drug release as a conversion of crystalline FF to amorphous form and ensured the chemical compatibility among FF and carriers. The results specified the significant improvement of FF release using solid dispersion technique.

Fenofibrate可减缓糖尿病患者的病情进展

法国Fournier制药公司的Jean-Claude Ansquer。博士及其同事报道说，fenofibrate(非诺贝特，FB)与2型糖尿病患者的脂类改善及微白蛋白尿症进展的减缓关联；但还需更进一步的研究以确定其对肾功能的长期作用。

Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway

Fenofibrate,a peroxisome proliferator-activated receptor α(PPARα)agonist,is widely prescribed for hyperlipidemia management.Recent studies also showed that it has therapeutic potential in various liver diseases.However,its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear.Here,the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice,which was dependent on hepatocyteexpressed PPARα.Yes-associated protein(YAP)is pivotal in manipulating liver growth and regeneration.We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination,promoting its K63-linked ubiquitination,and enhancing the interaction and transcriptional activity of the YAP-TEAD complex.Pharmacological inhibition of YAP-TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly.Other factors,such as MYC,KRT23,RAS,and RHOA,might also participate in fenofibrate-promoted hepatomegaly and liver regeneration.These studies demonstrate that fenofibratepromoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling,with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.

非诺贝特酸降脂疗效和安全性评价--一项中国区随机、双盲、安慰剂对照临床研究

目的:验证非诺贝特酸在中国人群中的降脂疗效和安全性。方法:采用多中心双盲随机对照试验设计,将不同类型的高脂血症患者分为重度、中度高甘油三酯血症(HTG)及混合型血脂异常(MD)3个队列,1:1随机化将不同队列患者分为非诺贝特酸组与安慰剂组,分别给予非诺贝特酸(135mg,每天1次)或安慰剂治疗12周,主要终点为甘油三酯(TG)从基线至治疗12周时的变化百分比,次要终点为其他血脂成分和高敏C反应蛋白的变化百分比,同时记录不良事件的发生情况。结果:重度(n=52)、中度(n=23)HTG和MD(n=52)三个队列患者中,非诺贝特酸组的TG水平从基线至治疗12周分别降低(49.12±29.19)%、(47.95±25.19)%和(49.79±19.28)%,安慰剂组分别降低(18.88±40.69)%、(8.11±29.86)%和升高了(10.42±73.04)%,非诺贝特酸组TG降低幅度与安慰剂组相比差异均有统计学意义(重度HTG队列P<0.017,中度HTG和MD队列P均<0.05)。非诺贝特酸组高密度脂蛋白胆固醇(HDL-C)升高(25.51±21.45)%、(24.55±24.73)%和(23.60±27.38)%,安慰剂组升高(1.91±20.42)%、(2.40±9.32)%和(7.13±19.12)%,差异均有统计学意义(P均<0.05)。非诺贝特酸组发生率>5%的不良事件包括上呼吸道感染(10.9%)、腹痛(6.3%)及血肌酐水平升高(6.3%),与安慰剂组比较发生率差异无统计学意义。结论:对于中国重度、中度HTG患者或已接受他汀类药物治疗的MD患者,非诺贝特酸可显著降低TG水平,并升高HDL-C水平,不良事件发生率与服用安慰剂相似。

非诺贝特对阿霉素诱导的肾病模型大鼠的肾脏保护作用及机制

目的 研究非诺贝特对阿霉素诱导的肾病模型大鼠血脂、肾脏功能和形态的改变以及氧化应激、炎症、凝血因子的影响,探讨非诺贝特的肾脏保护作用并分析其机制。方法 将30只雄性SD大鼠随机分为正常对照组、模型组和治疗组,分别于实验第1天、第7天尾静脉注射阿霉素4 mg/kg、2 mg/kg,制备肾病综合征大鼠模型,正常对照组尾静脉注射等量0.9%氯化钠溶液。造模第8周后,治疗组大鼠给予非诺贝特(60 mg/kg)水溶液灌胃,其余2组给予等量0.9%氯化钠溶液灌胃。观察3组大鼠的一般状态、饮食、尿量及体重等变化。收集大鼠24 h尿液,利用考马斯亮蓝法检测24 h尿蛋白定量。实验结束后留取肾组织及血液标本,HE染色观察肾组织病理改变,生化分析仪检测3组大鼠血清肌酐(CRE)、血尿素氮(BUN)、胆固醇(TC)、三酰甘油(TG)水平,试剂盒检测3组大鼠肾组织匀浆中丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平,酶联免疫吸附法检测血清C反应蛋白(CRP)和血浆纤维蛋白原(FG)水平。结果 与正常对照组比较,模型组大鼠一般状态差、体重逐渐减轻、24 h尿蛋白水平、血清CRE、BUN、TC、TG水平显著升高,肾小球及肾小管形态异常,表明肾病综合征大鼠模型制备成功;非诺贝特可显著改善肾病综合征模型大鼠的肾脏病理改变,治疗组大鼠体重较同期模型组普遍偏高,第8周时,2组间差异有统计学意义(P<0.01),24 h尿蛋白水平较同期模型组明显降低,第8周末更为显著(P<0.01),血清CRE、BUN、TC、TG水平显著降低,2组间差异均有统计学意义(P<0.05)。与模型组比较,治疗组大鼠肾组织中MDA含量显著降低,GSH-Px、SOD活性显著升高,血清CRP和血浆FG水平显著降低,差异均有统计学意义(P<0.05或<0.01)。结论 非诺贝特可能通过降低肾病综合征大鼠血脂及氧化应激、炎性因子和凝血因子的表达水平,对阿霉素诱导的肾病模型大鼠起到一定的肾脏保护作用。

硬脂酰辅酶A去饱和酶1通过抑制肺上皮细胞铁死亡缓解小鼠特发性肺纤维化进展的作用研究

目的 拟利用基因敲除小鼠和细胞系研究硬脂酰辅酶 A 去饱和酶 1(SCD1)在特发性肺纤维化(IPF)中的作用及机制。方法 利用SCD1条件敲除小鼠和BEAS-2B细胞,比较SCD1敲除或敲低后组织学改变和铁死亡变化,并研究PPARα激动剂Fenofibrate对SCD1表达和对IPF的影响。结果 敲除SCD1会加重IPF、上调纤维化相关蛋白水平并降低GPX4表达;敲低SCD1会提高脂质氧化水平、促进肺上皮细胞铁死亡,而Fenofibrate可上调SCD1表达,降低细胞铁死亡和IPF严重程度。结论 研究结果证实抑制SCD1会促进肺上皮细胞铁死亡、加重IPF,而Fenofibrate可通过上调SCD1表达治疗IPF。本研究将为防控IPF提供潜在靶点和候选药物。

非诺贝特对糖尿病小鼠视网膜神经组织中miR-26a-5p/PTEN表达的影响

目的:研究非诺贝特对糖尿病小鼠视网膜神经损伤的保护作用并观察其对miR-26a-5p及其靶基因PTEN的影响。方法:构建糖尿病小鼠模型,并进行非诺贝特灌胃,H&E及透射电镜观察视网膜神经损伤情况,Real-time PCR检测视网膜组织中miR-26a-5p的表达,Western blotting检测同源性磷酸酶-张力蛋白(PTEN)在视网膜组织中的表达,并观察NF-κB及IL-1β的水平及视网膜神经上皮的结构变化。结果:与糖尿病组相比,非诺贝特治疗组糖尿病小鼠视网膜神经节细胞损伤及神经纤维层萎缩明显减轻,视网膜中miR-26a-5p表达升高,PTEN mRNA和蛋白表达下降,炎性介质NF-κB及IL-1βmRNA表达水平下降(P<0.05)。结论:非诺贝特通过上调miR-26a-5p抑制PTEN的表达,降低炎症因子水平,减轻视网膜细胞损伤,发挥糖尿病视网膜神经保护作用。