姜黄素预处理对大鼠脑缺血/再灌注损伤的保护作用

目的 探讨姜黄素预处理对大鼠局灶性脑缺血/再灌注损伤的影响.方法 SD大鼠(♂)56只,随机分7组,为假手术组、模型组(0.154 mol·L-1生理盐水5 μl·g-1)、阳性对照组(尼莫地平0.4 μg·g-1)和药物治疗组(姜黄素20、40、60 μg·g-1)及溶媒对照组(DMSO),每组8只.药物治疗组在缺血前30 min分别腹腔注射相同体积的药物.局灶性脑缺血/再灌注损伤动物模型采用改良Longa线栓法制作.通过神经行为学评分、TTC染色法测定脑梗死面积和用实时定量RT-PCR对大鼠脑组织中BDNF mRNA的水平进行分析、酶联免疫吸附法(ELISA法)测定BDNF及其受体TrkB表达的方法,观察姜黄素预处理对大鼠脑缺血/再灌注损伤的保护作用.结果 和模型组相比,姜黄素组大鼠神经缺失症状有明显改善(P<0.05),脑梗死面积减小(P<0.05),脑组织中BDNF mRNA、BDNF及其受体TrkB的含量(P<0.05)明显提高.结论 姜黄素可降低行为学评分和脑梗死面积,增加大鼠脑缺血/再灌注损伤时BDNF mRNA、BDNF和其受体TrkB的表达水平,对脑缺血/再灌注损伤有保护作用.     

三七总皂甙对大鼠脑缺血再灌注损伤后p53蛋白表达的影响

目的 观察三七总皂甙对大鼠脑缺血再灌注损伤后p53蛋白表达的影响,探索三七总皂甙神经保护作用的分子机制.方法 采用SD大鼠局灶性脑缺血再灌注模型(transientmiddle cerebral arteryocclusion,MCAO),将大鼠随机分组,各组按实验设计给药造模,分时点对各组动物造模后神经功能缺陷进行评分,应用免疫组织化学法研究缺血再灌注损伤脑组织凋亡相关蛋白p53白表达情况.结果 PNS处理各组缺血再灌注后神经功能缺陷评分和脑组织p53蛋白表达均明显少于缺血再灌注组(P＜0.05).结论 三七总皂甙能减轻脑组织的缺血再灌注损伤,改善神经功能缺失.其作用机制可能与其抑制脑组织p53蛋白表达有关.     

羟乙葛根素对大鼠局灶性脑缺血再灌注损伤细胞凋亡及p53表达的影响

目的观察异黄酮类羟乙葛根素在大鼠局灶性脑缺血再灌注损伤时的抗凋亡作用。方法利用大鼠大脑中动脉栓线阻断法制备局灶性脑缺血再灌注损伤模型 ,利用病理学检查、免疫组织化学方法观察羟乙葛根素对缺血再灌注大鼠的脑组织细胞凋亡及p5 3表达的影响。结果羟乙葛根素能改善局灶性脑缺血再灌注损伤的病理学改变 ,减轻细胞凋亡的程度 ,抑制p5 3的表达。结论羟乙葛根素对大鼠局灶性脑缺血再灌注损伤具有保护作用 ,其作用机制可能与羟乙葛根素抗细胞凋亡 ,抑制p5 3表达有关。     

赤芍801对大鼠脑缺血/再灌注损伤后脑源性神经营养因子表达的影响

目的:探讨赤芍801(propyl gallate,PG)对大鼠局灶性脑缺血/再灌注损伤后神经功能损伤、细胞凋亡及脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达的影响。方法:线栓右侧大脑中动脉(middle cerebral artery,MCA)制成SD大鼠短暂局灶性脑缺血模型,实验大鼠随机分成:正常对照组、假手术组、模型组、溶媒组、PG组(分PG23.5、47、94μmol/kg3个亚组)等5组。采用Longa等评分法进行大鼠神经功能评分;TUNEL染色法观察缺血/再灌注不同时段(1、2、4、7d)模型鼠缺血区周边组织阳性神经元数量;免疫组织化学、蛋白免疫印迹法检测缺血/再灌注后不同时段各组缺血区周边组织BDNF的表达情况。结果:脑缺血/再灌注后1d,模型大鼠神经功能缺损评分、TUNEL阳性细胞数均达到高峰。与此相仿,该时段缺血周边区的BDNF表达亦达到高峰,此后逐渐下降。该时段TUNEL阳性细胞数和BDNF表达与其它各时段(2、4、7d)比较均有升高(P<0.01)。予上述不同剂量组的PG干预后,47、94μmol/kg组大鼠的神经功能缺损评分、T...     

杜仲提取物对大鼠脑缺血再灌注损伤的保护作用及其机制研究

目的 观察杜仲提取物对缺血再灌注损伤大鼠脑组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及诱导型一氧化氮合酶(iNOS)mRNA表达的影响。方法 采用大鼠大脑中动脉线栓法制备局灶性脑缺血再灌注损伤模型,造模前以杜仲提取物不同剂量连续ig给药14 d,缺血2 h,再灌注24 h后,观察杜仲提取物对脑缺血再灌注损伤大鼠神经功能症状,脑梗死范围改变,实时荧光定量PCR(RT-PCR)法检测脑缺血再灌注损伤大鼠海马TNF-α、IL-1β及iNOS mRNA的表达。结果 杜仲提取物可显著改善脑梗死范围(P<0.05),下调海马TNF-α、IL-1β及iNOS mRNA的表达(P<0.05)。结论 杜仲提取物可下调大鼠脑组织中TNF-α、IL-1β及iNOS mRNA的表达产生抗局灶性脑缺血再灌注损伤作用。     

葛根素对大鼠脑缺血/再灌注损伤缺血区细胞粘附分子ICAM-1的影响

目的探讨葛根素对大鼠脑缺血/再灌注损伤缺血区细胞粘附分子ICAM-1的影响。方法采用模拟临床上缺血性卒中的大鼠中脑动脉阻塞局灶性脑缺血/再灌注模型,预先给予葛根素腹腔注射7d后,运用免疫组织化学方法 ,检测大鼠脑缺血/再灌注损伤脑组织中ICAM-1蛋白的表达。结果葛根素能明显降低脑组织缺血区血管内皮细胞ICAM-1蛋白的表达,与模型组相比差异有统计学意义（P〈0.01）。结论葛根素能明显抑制大鼠局灶性脑缺血/再灌注所致炎症反应,对大鼠脑缺血-再灌注造成的脑血管内皮损伤具有明显保护作用。     

片仔癀对局灶性脑缺血/再灌注大鼠皮质中NMDAR1和GluR2表达的影响

目的研究片仔癀对局灶性脑缺血/再灌注大鼠皮质中NMDAR1、GluR2 mRNA及蛋白表达的影响。方法健康成年♂SD大鼠40只,随机分为假手术组、模型对照组、片仔癀给药组,用线栓法建立局灶性脑缺血/再灌注大鼠模型(MCAO)。Zea-Longa标准评分法评价大鼠神经功能损伤;TTC染色法评价脑梗死体积变化;qPCR法和Western blot法分别检测大鼠缺血侧脑组织皮质中NMDAR1、GluR2 mRNA及蛋白的表达。结果与MCAO组比较,片仔癀能明显改善大鼠的神经功能损伤,降低大鼠脑梗死体积,促进NMDAR1、GluR2 mRNA及蛋白的表达。结论片仔癀可能通过抑制局灶性脑缺血/再灌注大鼠皮质NMDAR1、GluR2 mRNA及蛋白的下调而发挥脑保护作用。     

右美托咪定预处理对局灶性脑缺血/再灌注星形胶质细胞胶质纤维酸性蛋白表达的影响

目的 探讨预注右美托咪定对局灶性脑缺血/再灌注后星形胶质细胞胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)表达的影响。方法 大脑中动脉插线法制作大鼠局灶性脑缺血/再灌注模型。观察脑缺血2 h再灌注24 h后神经功能损害改变并评分,并采用免疫组化和蛋白免疫印迹方法观察大鼠脑缺血后星形胶质细胞GFAP蛋白表达情况。结果 缺血/再灌注后可诱导大鼠脑组织星形胶质细胞GFAP表达明显增强,右美托咪定可明显改善大鼠神经功能损害,减少缺血区GFAP阳性星型胶质细胞,降低GFAP表达水平。结论 早期应用右美托咪定可抑制脑缺血后星形胶质细胞GFAP的过度表达,可发挥抗脑缺血损伤,保护神经元作用。     

组织自发荧光在大鼠局灶性脑缺血/再灌注损伤中的应用

目的基于特定的荧光检测技术,探讨组织自发荧光在大鼠局灶性脑缺血及再灌注损伤中的应用。方法本研究通过caliper精诺真IVIS活体成像技术检测大鼠脑组织的自发荧光。通过荧光检测,比较正常大鼠和局灶性脑缺血/再灌注损伤大鼠脑组织对应部位自发荧光强弱的变化,并进行定量分析。结果实验结果表明,局灶性脑缺血/再灌注损伤脑组织的自发荧光发生了明显变化,损伤部位的自发荧光信号明显增强,将荧光信号通过活体成像系统进行定量,与正常脑组织比较差异有统计学意义,P<0.01。结论大鼠脑组织在局灶性脑缺血/再灌注损伤后,脑组织的自发荧光明显增强,为大鼠局灶性脑缺血/再灌注损伤模型的研究及其评价提供新的方法。     

白藜芦醇保护脑缺血/再灌注损伤与自噬关系的研究

目的研究白藜芦醇(resveratrol,Res)预处理对大鼠局灶性脑缺血/再灌注损伤后自噬的影响,探讨Res保护局灶性脑缺血/再灌注损伤的作用机制。方法将64只SD♂大鼠随机分成4组,假手术组(S组)、模型组(M组)、Res低剂量(15 mg.kg-1)干预组(R1组)和Res高剂量(40 mg.kg-1)干预组(R2组),用线栓法制备大鼠大脑中动脉栓塞(MCAO)模型,缺血2 h,再灌注24 h后,观察大鼠神经功能评分;透射电镜法观察神经元的超微结构及其内自噬空泡数量的变化;免疫组化法检测LC3的蛋白表达;RT-PCR法分别检测LC3和Beclin 1的mRNA表达。结果与M组相比,Res可明显减轻大鼠脑缺血/再灌注损伤的神经功能评分(P<0.05);使自噬泡数量明显增加;上调缺血皮质区脑组织LC3和Beclin 1蛋白及mRNA的表达(P<0.05)。结论 Res对大鼠局灶性脑缺血/再灌注损伤后神经元有保护作用,其机制可能与其诱导自噬的生成,上调LC3和Beclin 1的表达有关。     

The effect of icariin on promoting neurogenesis and angiogenesis and its mechanism

OBJECTIVE To observe the effects of icariin(ICA) on neurogenesis and angiogenesis after ischemia,and investigate the possible mechanism.METHODS The rats were subjected to middle cerebral artery occlusion(MCAo)-reperfusion injury with thread embolus,24 h later ICA was intragastrically administrated to rats at doses of 20,40 and 80 mg·kg-1 once a day,respectively,continuously for 28 d.The behavioral test was performed using the neurological severity score(NSS) 18 scores at 24,72 h,7,14,21 and 28 d after ischemia,resepectively.Rats were sacrificed 28 d after MCAo,infarct volume was evaluated by TTC staining.The mRNA expression of brain-derived neurotrophic factor(BDNF) and its receptor TrkB and VEGF and its receptor VEGFR2 were detected by RT-PCR,and the protein expression of BDNF,TrkB,VEGF and VEGFR 2 were determined by Western blotting.RESULTS ICA obviously attenuated neurological functional deficit score,as well as infarction volume.ICA raised the number of BrdU/NeuN and BrdU/GFAP positive cells in the ischemia periphery zone of rats 28 d after ischemia.At the same time,ICA noticeablely enhanced the mRNA expression of VEGF,VEGFR2,BDNF and TrkB,and the protein expression of VEGF and BDNF and TrkB were increased 28 d after ischemia.CONCLUSION The results showed that ICA may promote neurogenesis and angiogenesis after ischemia in rats,and the possible mechanism might be,at least partly,due to an increase of BDNF and its receptor TrkB,VEGF and its receptor VEGFR2 in the brain.     

Nrf2调控AIM2炎症小体在大鼠脑缺血再灌注 损伤中的作用

目的 探讨核因子E2相关因子2（Nrf2）对脑缺血再灌注损伤的影响及对黑色素瘤缺乏因子2（AIM2）炎症 小体的调控作用。方法 将108只雄性SD大鼠按随机数字表法分为假手术组（Sham组）、脑缺血再灌注模型组（I/R 组）、Nrf2抑制剂鸦胆子苦醇（Bru）干预组（Bru组），每组再按随机数字表法进一步分为脑缺血再灌注后8、24、72 h组， 共9组，每组12只。I/R组和Bru组采用线栓法建立大脑中动脉栓塞（MCAO）模型。于相应时间点对各组行神经功能 缺损评分；采用2，3，5-氯化三苯基四氮唑（TTC）染色测定脑梗死面积；HE染色检测脑组织病理损伤；荧光定量PCR 法检测缺血侧脑组织中AIM2 mRNA表达；Western blot法检测缺血区脑组织中AIM2、Nrf2蛋白的表达；酶联免疫吸 附试验法检测缺血区脑组织中凋亡相关斑点样蛋白（ASC）、半胱氨酸蛋白酶（Caspase）-1、白细胞介素（IL）-1β和IL-18 的表达。结果 与Sham组比较，I/R组各时间点神经功能缺损评分升高，脑组织病理损伤显著加重，AIM2 mRNA以 及Nrf2、AIM2、ASC、Caspase-1、IL-1β、IL-18蛋白表达水平升高（P＜0.05）。与I/R组比较，Bru组各时间点神经功能 缺损评分升高，脑组织病理损伤更重，Nrf2蛋白表达水平降低，AIM2 mRNA和蛋白，ASC、Caspase-1、IL-1β、IL-18蛋 白表达水平升高（P＜0.05）。结论 Nrf2在脑缺血再灌注损伤中具有内源性神经保护作用，其机制可能与Nrf2可负 性调控AIM2炎症小体，减少炎性细胞因子的释放有关。     

Effect of active components group of Xiaoxuming decoction on cerebral mitophagy after focal cerebral ischemia/reperfusion injury

OBJECTIVE To explore the effect of the active components group of Xiaoxuming decoction(XXMD)on mitophagy after cerebral ischemia/reperfusion(I/R) in MCAO rats. METHODS Male Sprague-Dawley rats were randomly divided into 4 groups: sham group, XXMD and rapamycin group. The I/R models were induced by middle cerebral artery occlusion. The effects of XXMD and rapamycin on behavioral study of focal cerebral I/R in rats were measured by Zea-Longa′ s level standard scoring method and neurological defect score(m NSS). The volume percentage and hemispheric swelling of rat cerebral infarction were detected by TTC staining. Proteins in the mitophagy were detected by Western blotting. RESULTS The behavioral results showed that compared with the model group, XXMD decoction and rapamycin could significantly alleviate the neurological deficit scores after I/R, decreased the m NSS score(P<0.05) of the MCAO rats. TTC results showed that XXMD and rapamycin could significantly reduce the percentage of infarct volume and hemispheric swelling(P<0.05) of MCAO rats. Compared with the model group, the XXMD could significantly inhibit the expression of P62, Beclin-1 and BNIP3 and decrease LC3-Ⅱ/LC3-Ⅰ ratio(P<0.05, P<0.01) in isolated cerebral mitochondrial proteins at 24 h after cerebral I/R. However, the expression of P62,Beclin-1, BNIP3(P<0.05, P<0.01) and the ratio of LC3-Ⅱ/LC3-Ⅰin purified mitochondrial proteins can be significantly elevated by XXMD at 96 h after cerebral I/R. CONCLUSION Autophagy and mitophagy were activated at 24 h after cerebral I/R, and then it was inhibited. XXMD can protect mitochondrial structures, regulate the level of mitophagy at different points after cerebral I/R, inhibit the excessive activation of mitophagy in 24 h after I/R, and improve the level of mitophagy in the later stage of I/R.     

Clinically relevant doses of fluoxetine and reboxetine induce changes in the TrkB content of central excitatory synapses.

We have studied the effect of low doses of two widely used antidepressants, fluoxetine (Flx) and reboxetine (Rbx), on excitatory synapses of rat brain cortex and hippocampus. After 15 days of Flx treatment (0.67 mg/kg/day), its plasma level was 20.7+/-5.6 ng/ml. Analysis of postsynaptic densities (PSDs) by immunoblotting revealed no changes in the glutamate receptor subunits GluR1, NR1, NR2A/B, mGluR1alpha nor in the neurotrophin receptor p75(NTR). However, the brain-derived neurotrophic factor (BDNF) receptor TrkB decreased by 42.8+/-6%, and remained decreased after 6 weeks of treatment. The BDNF and TrkB content in homogenates of cortex and hippocampus began to rise at 9 and 15 days, respectively, and remained high for up to 6 weeks. Similar results were obtained following chronic Rbx administration at 0.128 mg/kg/day. We propose that BDNF, whose synthesis is increased by antidepressants, and which is in part released at synaptic sites, binds to TrkB in PSDs, leading to the internalization of the BDNF-TrkB complex and, thus, to a decrease of TrkB in the PSDs. This was paralleled by greater levels of phosphorylated (ie activated) TrkB in the light membrane fraction, that contains signaling endosomes. The retrograde transport of endocyted BDNF/TrkB complexes from spines to cell bodies, where it activates the synthesis of more BDNF, is a protracted process, potentially requiring several cycles of TrkB/BDNF complex endocytosis and transport. This positive feedback mechanism may help explain the time-lag between drug administration and its therapeutic effect, that is, the antidepressant drug paradox.     

曲唑酮对脑卒中后抑郁大鼠学习记忆功能及海马区BDNF、受体TrkB表达的影响

目的：探讨曲唑酮对脑卒中后抑郁大鼠学习记忆功能及海马区脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）、受体酪氨酸激酶B（TrkB）蛋白表达的影响。方法：选取雄性SD大鼠72只随机分为6组（对照组、模型对照组、阳性对照组、曲唑酮小、中、大剂量组）,每组均为12只。选择右侧大脑中动脉进行栓塞,并连续给予慢性无法预见性的应激（3周）建立大鼠卒中后抑郁模型（对照组除外）。在给予慢性应激的同时,曲唑酮小、中、大剂量组分别给予曲唑酮（8,13,20 mg·kg^-1）灌胃,阳性对照组给予文拉法辛（20 mg·kg^-1）灌胃,均每天1次,连用21 d。Morris水迷宫试验对大鼠空间学习记忆功能进行评价,免疫组化法对海马区BDNF表达进行检测。免疫印迹法对BDNF及其受体TrkB蛋白表达进行检测。结果：模型组、曲唑酮中剂量组、大剂量组在用药第7,14,21天大鼠糖水偏爱情况与模型对照组比较,差异有显著性（P<0.05）;大剂量组在用药第14天、第21天大鼠糖水偏爱情况与小剂量组比较,差异有显著性（P<0.05）;曲唑酮小、中、大剂量组逃避潜伏期、穿平台次数、空间探索时间与模型对照组比较,差异均有显著性（P<0.05）;中、大剂量组逃避潜伏期、穿越平台次数、空间探索时间与小剂量组比较,差异有显著性（P<0.05）;模型对照组BDNF、TrkB阳性细胞数明显低于对照组（P<0.05）;曲唑酮小、中、大剂量组BDNF、TrkB阳性细胞数、BDNF及TrkB蛋白表达明显高于模型对照组（P<0.05）;大剂量组BDNF、TrkB阳性细胞数、BDNF及TrkB蛋白表达明显高于小、中剂量组（P<0.05）。结论：大、中、小剂量曲唑酮能改善脑卒后抑郁大鼠的空间学习及记忆功能,以大剂量曲唑酮效果最明显,其作用机制可能与同时上调海马BDNF及其受体TrkB的表达有关。     

苦碟子注射液对大鼠急性脑缺血-再灌注损伤的保护作用

目的观察苦碟子注射液对脑缺血-再灌注损伤的保护作用并探讨其可能机制。方法用线栓法制作大鼠大脑中动脉栓塞模型(MCAO)。大鼠随机分成假手术组(sham)、脑缺血-再灌注损伤组(I/R)和苦碟子保护组(KD)。观察神经功能学评分,形态学观察(光镜和电镜),如脑梗塞面积(HE染色)及测定脑组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果苦碟子注射液可降低缺血-再灌注损伤后的神经功能学评分、脑梗死面积、缺血脑组织丙二醛含量,减轻形态结构损伤,提高超氧化物歧化酶活性。结论苦碟子注射液对于脑缺血-再灌注损伤有一定的保护作用,其作用机制与清除氧自由基和抗脂质过氧化有关。     

牡荆素通过12/15-LOX信号通路减轻大鼠脑缺血再灌注损伤的研究

目的探讨牡荆素对大鼠大脑中动脉缺血再灌注损伤的保护作用及可能机制。方法 60只雄性SD大鼠随机分为假手术组、模型组及牡荆素40、80 mg/(kg·d)组,每组15只。制作大鼠大脑中动脉缺血(90 min)/再灌注(24 h)损伤模型。术前1周及模型制作前30 min,各组分别ip相应药物,假手术组和模型组给予等量生理盐水。观察牡荆素对神经功能缺损评分、脑指数及梗死体积的影响,采用激光多普勒血流仪监测再灌注后大鼠缺血侧局部脑血流量的动态变化,测定缺血侧脑组织活性氧(ROS)水平、超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量、Caspase-3活性及12羟二十烷四烯酸(12-HETE)、15羟二十烷四烯酸(15-HETE)含量;实时荧光定量PCR检测Bcl-2、Bax、ALOX15 mRNA的表达,Western blotting检测ALOX15蛋白、p38MAPK及p-p38MAPK蛋白表达。结果与假手术组相比,模型组大鼠神经缺失症状评分、脑指数及梗死体积显著升高(P<0.01),ALOX15 mRNA和蛋白的表达及p38MAPK和p-p38MAPK蛋白表达显著增加(P<0.01),同时Caspase-3活性、Bax mRNA表达明显升高(P<0.01),而Bcl-2 mRNA表达显著下降(P<0.01)。与模型组比较,牡荆素预处理能能显著改善模型大鼠神经功能缺损症状,降低脑指数,减少梗死体积,增加缺血侧大脑局部血流量,明显增加缺血侧脑组织Bcl-2m RNA表达(P<0.05、0.01),提高SOD活性(P<0.05、0.01),降低ALOX15 mRNA、Bax mRNA和ALOX15、p38MAPK和p-p38MAPK蛋白表达(P<0.05、0.01),下调Caspase-3活性、15-HETE、12-HETE的表达和MDA水平(P<0.05、0.01)及减少ROS的生成(P<0.05、0.01)。结论牡荆素对局灶性缺血大脑具有神经保护作用,并可改善缺血侧大脑血流供应。其作用机制可能为通过12/15-LOX信号抑制p38MAPK介导的细胞凋亡,同时降低氧化应激和炎症,从而减轻脑I/R损伤。     

Propolis ameliorates cerebral injury in focal cerebral ischemia/reperfusion (I/R) rat model via upregulation of TGF-β1

Neuroprotective impact of transforming growth factor β1 (TGF-β1) is increasingly recognized in different brain injuries. Propolis exhibits a broad spectrum of biological and pharmacological properties including neuroprotective action. The objective of the investigation was to explore the involvement of TGF-β1 signaling in the neuroprotective mechanism of propolis in I/R rats. In this study, focal cerebral ischemia model was built by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The investigation was carried out on 48 rats that were arranged into four groups (n = 12): the sham group, I/R control group, I/R + propolis (50 mg/kg) group and I/R + propolis (100 mg/kg) group. The results revealed that propolis preserved rats against neuronal injury induced by cerebral I/R. It significantly reduced neurological deficit scores and improved motor coordination and locomotor activity in I/R rats. Propolis antagonized the damage induced by cerebral I/R through suppression of malondialdehyde (MDA) and elevation of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), brain-derived neurotropic factor (BDNF) and dopamine levels in the brain homogenates of I/R rats. Other ameliorations were also observed based on reduction of neurodegeneration and histological alterations in the brain tissues. These results also proposed that the neuroprotective effect of propolis might be related to upregulation of TGF-β1 and suppressed matrix metallopeptidase-9 (MMP9) mRNA expression.