逍遥散对慢性应激大鼠海马组织DUSP14基因表达及对MAPK信号通路的影响

目的：探讨逍遥散对慢性应激大鼠海马组织双特异性磷酸酶 14 （DUSP14） mRNA 表达及对 p38 丝裂原活化蛋白激酶（p38 MAPK）、c-Jun 氨基末端蛋白激酶（JNK）、细胞外信号调节蛋白激酶（ERK）、细胞外信号调节蛋白激酶 5（ERK5）等四类丝裂原活化蛋白激酶 （MAPKs） 信号通路活化状态的影响。方法：将 80 只大鼠分为空白组、模型组、氟西汀组及逍遥散组。空白组大鼠常规饲养,每天灌胃 2 mL 生理盐水;模型组大鼠每天灌胃 2 mL 生理盐水后进行慢性应激刺激;氟西汀组和逍遥散组分别灌胃氟西汀和逍遥散后进行慢性应激刺激;剂量均为 10 mL/（kg · d）。检测各组大鼠海马组织 DUSP14 mRNA 表达及p38、磷酸化 p38 （p-p38）、JNK、磷酸化 JNK （p-JNK）、ERK、磷酸化 ERK （p-ERK）、ERK5、磷酸化 ERK5 （p-ERK5） 的相对含量。结果：与空白组比较,模型组 DUSP14 mRNA 表达显著上调 （P＜0.01）,p-p38/p38、p-JNK/JNK、p-ERK5/ERK5 均显著升高 （P＜0.01）,p-ERK/ERK 显著降低 （P＜0.01）。与模型组比较,逍遥散组和氟西汀组 DUSP14 mRNA 表达均下调 （P＜ 0.01）;逍遥散组 p-p38/p38、p-JNK/JNK 显著降低（P＜0.01）,p-ERK/ERK 显著升高（P＜0.01）;氟西汀组 p-p38/p38、p-JNK/JNK、p-ERK5/ERK5 均显著降低 （P＜0.01）,p-ERK/ERK 显著升高 （P＜0.01）。与氟西汀组比较,逍遥散组 p-JNK/JNK、p-ERK5/ERK5 均较高（P＜0.05,P＜0.01）。结论：逍遥散和氟西汀对慢性应激引起的 DUSP14 mRNA 表达变化及 MAPK 各信号通路活性变化的调节作用趋势基本一致,对 p38 MAPK 信号通路的调节作用相当,但在 ERK5 MAPK 通路中逍遥散未表现出活性调节作用,在 ERK、JNK MAPK 通路活化状态调节过程中氟西汀更显优势。     

糖络宁浸膏对糖尿病大鼠周围神经氧化应激及下游MAPKs信号转导通路的影响

目的探讨糖络宁浸膏治疗糖尿病周围神经病变的可能作用机制。方法采用一次性腹腔内注射大剂量链脲佐菌素(60 mg/kg)诱导糖尿病大鼠模型。将造模成功大鼠随机分为模型组、中药组、西药组,每组23只,另设健康大鼠15只为正常组。中药组予糖络宁浸膏按生药20 g/(kg·d)灌胃,西药组予α-硫辛酸20 mg/(kg·d)灌胃,正常组和模型组大鼠予等体积蒸馏水灌胃,连续12周。观察各组大鼠血清和坐骨神经中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,大鼠背神经根节(DRG)p38 MAPK、pp38 MAPK、p46JNK、p-p46JNK、ERK1/2、p-ERK1/2蛋白表达。结果与正常组比较,模型组大鼠血清、坐骨神经SOD活性显著降低,而MDA含量均显著增多(P0.01);与模型组比较,中药组和西药组大鼠血清、坐骨神经SOD活性均显著增强,MDA含量均显著减少(P0.01)。各组大鼠DRG的p38 MAPK、p46JNK、ERK1/2总蛋白表达量相近,组间比较差异均无统计学意义(P0.05);与正常组比较,模型组大鼠DRG的p-p38 MAPK、p-p46JNK、p-ERK1/2活性蛋白表达均明显增高(P0.05),而中药组、西药组大鼠DRG的p-p38 MAPK、p-p46JNK、p-ERK1/2活性蛋白表达均较模型组明显减弱(P0.05)。结论糖络宁浸膏具有显著降低糖尿病大鼠血清、坐骨神经MDA含量,提高血清、坐骨神经SOD活性的作用,有效抑制糖尿病大鼠DRG的p-p38 MAPK、p-p46JNK、p-ERK1/2活性蛋白表达,从而抑制氧化应激反应,对MAPK信号转导通路具有负性调控作用。     

眼针对脑缺血再灌注损伤模型大鼠MAPK信号转导通路的影响

目的:观察眼针对脑缺血再灌注损伤模型大鼠脑缺血半暗带组织中MAPK信号转导通路的变化,探讨其作用机制。方法:健康SPF级雄性SD大鼠200只,体重(280±20)g。按体重随机分组,分为空白对照组(15只)、假手术组(40只)和模型复制组(145只)。对模型复制组145只大鼠采用线栓法进行模型复制,模型评价后,筛选模型合格的大鼠进行亚组划分,分别为模型对照组、眼针对照组。即共分为4组:正常组、假手术组、模型组、眼针组。给予眼针组大鼠再灌注即刻进行针刺治疗之后每8 h进行一次针刺治疗,至再灌注3 h、24 h、72 h,分别取材进行相关指标检测。采用Western-blot法检测各组大鼠半暗带脑组织中磷酸化P38MAPK、ERK1/2和JNK蛋白表达水平。采用RT-PCR法检测各组大鼠半暗带脑组织中P38MAPK、ERK1/2和JNK mRNA表达水平。结果:与空白对照组比较,模型对照组和眼针组大鼠脑组织中P38MAPK、ERK1/2、JNK磷酸化水平及其mRNA表达水平均显著升高(P0.01);与模型对照组比较,眼针组大鼠脑组织中P38MAPK、ERK1/2、JNK磷酸化水平及其mRNA表达水平显著下降(P0.05)。结论:眼针可能通过抑制p38-MAPK信号转导通路而发挥其脑保护作用。     

清肺通络膏对大鼠呼吸道合胞病毒肺炎肺组织MAPK信号通路的影响

目的:通过观察清肺通络膏及其拆方对大鼠呼吸道合胞病毒肺炎肺组织MAPK信号通路的影响,探讨清肺通络膏对大鼠呼吸道合胞病毒肺炎的防治机制。方法:以呼吸道合胞病毒滴鼻感染大鼠,治疗组分别予清肺通络膏全方、主药和辅药干预。感染病毒后第7天,实时荧光定量PCR(real time RT-PCR)检测大鼠肺组织中p38、ERK、JNK m RNA的含量,western blot的方法观察肺组织中p-p38、p-ERK、p-JNK蛋白水平。结果:正常组和模型组肺组织中均可检测到p38、ERK2、JNK1 m RNA表达及p-p38、p-ERK、p-JNK蛋白表达,但模型组明显高于正常组(P0.05)。治疗组中清肺通络膏全方组p38、ERK2、JNK1 m RNA表达及p-p38、p-ERK、pJNK蛋白表达最低,与主药组、辅药组比较有显著性差异(P0.05)。结论:呼吸道合胞病毒感染大鼠时激活了MAPK信号通路,清肺通络膏全方组能较好的抑制MAPK信号通路的活化,且优于主药及辅药组。     

知葛通脉汤对糖尿病周围神经病变大鼠背根神经节MAPK / ERK通路的影响

目的:研究知葛通脉汤对糖尿病周围神经病变背根神经节丝裂原活化蛋白激酶(MAPK)/细胞外调节蛋白激酶(ERK)通路的影响。方法:选取无特定病原体级SD雄性大鼠50只为研究对象,随机选取10只作为对照组,其余40只为研究组,随机分为四组:知葛通脉汤低、中、高剂量组:分别按照每日2.5g/kg、7.5g/kg、15g/kg体重标准灌胃知葛通脉汤,模型组灌胃给予等量生理盐水,连续给药6周,观察记录大鼠背根神经节中磷酸化p38MAPK(p-p38MAPK)、p38MAPK、ERK、磷酸化ERK(p-ERK)活性和表达水平以及p38MAPK、ERKmRNA水平。结果:模型组p-p38MAPK、p-ERK活性和蛋白表达水平明显高于对照组,差异有统计学意义(P0.05);知葛通脉汤低、中、高剂量组p-p38MAPK、p-ERK活性和蛋白表达水平明显低于模型组(P0.05);知葛通脉汤高剂量组p-p38MAPK、p-ERK活性和蛋白表达水平明显低于低剂量组(P0.05),各组之间p38MAPK、ERK活性和蛋白表达水平无明显差异(P0.05);模型组p38MAPK、ERKmRNA表达水平明显高于对照组,差异有统计学意义(P0.05);知葛通脉汤低、中、高剂量组p38MAPK、ERKmRNA表达水平明显低于模型组(P0.05);知葛通脉汤高剂量组p38MAPK、ERKmRNA表达水平明显低于低剂量组(P0.05)。结论:知葛通脉汤可降低p-p38MAPK、p-ERK活性和蛋白表达水平,有效抑制背根神经节MAPK/ERK通路。     

柴朴汤对哮喘模型大鼠气道炎症及ERK/p38 MAPK信号通路的影响

目的:观察柴朴汤对哮喘模型大鼠气道炎症及细胞外信号调节激酶(ERK)/p38丝裂原活化蛋白激酶(p38MAPK)信号通路的影响。方法:SD大鼠随机分为空白组、模型组、柴朴汤低、中、高(0.75,1.5,3.0 g·kg-1)组,地塞米松组。采用卵蛋白(OVA)致敏激发建立大鼠哮喘模型。柴朴汤低、中、高剂量组于激发前0.5 h给予相应剂量柴朴汤灌胃;地塞米松组于激发前0.5 h给予地塞米松(0.005 g·kg-1)灌胃;模型组于激发前0.5 h给予等体积生理盐水灌胃;空白组以生理盐水代替OVA进行腹腔注射及雾化吸入;隔日1次,共激发28 d。观察各组大鼠支气管肺泡灌洗液(BALF)中细胞总数及分类细胞计数的变化;酶联免疫吸附法(ELISA)检测肺组织磷酸化ERK(p-ERK),磷酸化p38 MAPK(p-p38 MAPK)的活性;实时荧光定量PCR(Real-time PCR)分析检测ERK,p38 MAPK mRNA的表达;蛋白免疫印迹法(Western blot)检测ERK,p-ERK,p38MAPK,p-p38 MAPK蛋白的表达;光镜下观察病理组织形态学变化及进行炎症评分。结果:模型组大鼠BALF中细胞总数和分类细胞计数;肺组织p-ERK,p-p38 MAPK的活性,ERK,p38 MAPK mRNA的表达,p-ERK,p-p38 MAPK的表达,炎症评分均明显高于空白组(P0.01);柴朴汤低、中、高剂量组和地塞米松组上述指标则明显低于模型组(P0.05,P0.01)。结论:柴朴汤可改善哮喘模型大鼠气道炎症,其机制可能与其抑制ERK/p38 MAPK信号通路有关。     

苦参颗粒对兔耳痤疮模型P38MAPK/ERK相关信号通路的影响

目的:探讨苦参颗粒溶液对兔耳痤疮模型P38MAPK/ERK相关信号通路的影响及其治疗效果。方法:家兔除空白对照组外,其余各组用kligman法建立兔耳痤疮模型,于造模成功后,予模型组、夫西地酸乳膏组、苦参颗粒100、200、400mg/ml组分别涂敷生理盐水和相应药物,每日一次,连续14d。通过HE染色显微镜下判断其治疗效果;免疫组化检测TNF-α、IL-6、IL-8蛋白的表达;Western blot法检测p-p38MAPK、p-ERK、p38MAPK、ERK蛋白表达;ELISA测定法p-p38MAPK、p-ERK蛋白的含量。结果:与空白组比较,模型组TNF-α、IL-6、IL-8 MOD值和p-p38MAPK、p-ERK表达明显升高,p38MAPK、ERK表达明显下降;与模型组相比,给药各组TNF-α、IL-6和IL-8 MOD值和p-p38MAPK、p-ERK表达明显降低,p38MAPK、ERK表达明显增加。结论:苦参颗粒溶液能降低TNF-α、IL-6、IL-8含量,下调p-p38MAPK、p-ERK蛋白表达,上调p38MAPK、ERK蛋白表达,干预ERK、p38MAPK通路,从而干预痤疮的形成,对痤疮有疗效。     

搜风愈喘方基于ERK/p38MAPK 信号通路对支气管哮喘模型大鼠气道炎症的作用机制探讨

目的 探讨祛风、化痰、活血法并施的搜风愈喘方对哮喘大鼠气道炎症的作用机制以及对ERK/p38MAPK信号通路的调节作用。方法 将32只SD大鼠随机分为正常组、模型组、地塞米松组、搜风愈喘方组。先以卵蛋白（OVA）致敏及雾化激发制备哮喘大鼠模型。造模成功后,各组大鼠给予相应药物干预治疗21d。ELISA法检测血清及肺泡灌洗液（BALF）中的白细胞介素13(IL-13）、肿瘤坏死因子α(TNF-α）含量;HE染色、PAS染色观察大鼠肺组织病理形态学变化;RT-PCR法检测肺组织匀浆中IL-13、ERK1、ERK2、p38MAPK的mRNA表达;Western Blot法检测肺组织中ERK、p-ERK、p-38MAPK、p-p38MAPK的表达。结果 ELISA法测定结果显示,与正常组比较,模型组血清中IL-13、TNF-α的含量升高（P<0.05）,肺组织中IL-13、ERK1、ERK2、p38MAPK的mRNA表达及p-ERK、p-38MAPK的蛋白表达均明显增强（P<0.05）;与模型组相比,地塞米松组及搜风愈喘方组可降低血清中IL-13、TNF-α的含量、肺组织中I...     

眼针八区八穴对脑缺血再灌注24h大鼠海马组织中MAPK信号传导通路的影响

目的:观察八区八穴取穴眼针疗法对脑缺血再灌注损伤模型大鼠海马组织中p38MAPK、ERK1/2、JNK表达水平的影响,探讨八区八穴取穴眼针疗法治疗缺血性脑病的部分机制。方法:健康SPF级雄性SD大鼠40只,体质量(280±20)g。按体质量随机分组,分为空白对照组(8只)、假手术组(8只)和模型复制组(24只)。对模型复制组24只大鼠采用线栓法进行模型复制,模型评价后,筛选模型合格的大鼠进行亚组划分,分别为模型对照组、眼针对照组,即分为正常组、假手术组、模型组、眼针组4组。眼针组大鼠给予眼针干预,再灌注即刻以及之后的每8 h进行1次针刺治疗,至再灌注24 h取材进行相关指标检测。采用免疫组织化学法检测各组大鼠海马组织中P38MAPK、ERK1/2和JNK蛋白表达水平。结果:与空白对照组比较,模型对照组和眼针组大鼠海马组织中P38MAPK、ERK1/2、JNK蛋白表达水平均显著升高;与模型对照组比较,眼针组大鼠脑组织中P38MAPK、ERK1/2、JNK蛋白表达水平显著下降。结论:眼针可能通过抑制p38-MAPK信号传导通路而发挥其脑保护作用。     

miR-145抑制VSMC增殖的作用及其相关信号通路研究

目的探讨miR-145对PDGF—BB诱导的大鼠原代血管平滑肌细胞（VSMC）的作用及丝裂原激活的蛋白激酶（MAPK）信号转导途径的作用。方法体外培养大鼠原代VSMC,再将细胞分为空白对照组、miR—NC组、PDGF—BB＋miR-145组及PDGF—BB组。CCK-8法检测各组细胞的增殖情况;实时RT—PCR方法检测PCNA、c—Jun及SM22a的表达水平;Western印迹方法检测ERK1／2和P—ERK1／2的表达、JNK和P—JNK的表达以及p38MAPK和P—p38MAPK的表达。结果miR-145过表达后能够抑制PDGF诱导的大鼠原代VSMC增殖,并下调VsMc增殖相关基因PCNA、c—Jun的表达、上调分化相关基因SM22a的表达;PDGF—BB诱导VSMC后,ERK、JNK、p38MAPK的磷酸化水平均明显上调,而转染miR-145慢病毒后再加PDGF刺激,ERK、JNK、p38MAPK的磷酸化水平均明显下调。结论miR-145能够抑制去分化型VSMC中的MAPK信号通路,进而抑制VSMC的增殖。     

川芎嗪预处理对心肌缺血再灌注损伤大鼠p38MAPK和TNF-α表达的影响

目的：探讨川芎嗪预处理对心肌缺血再灌注损伤的保护作用及机制。方法：30只Wistar大鼠被随机分为3组：假手术组、缺血再灌注损伤（IR）组、川芎嗪预处理组（LI）。建立大鼠心肌缺血再灌注损伤模型，应用酶联免疫吸附法，测定心肌TNF-α和IL-6水平；用免疫组化S-P法，检测p38MAPK蛋白的表达。结果：LI组与IR组比较，TNF-α、IL-6均显著降低（P〈0．01），p38MAPK蛋白阳性表达显著减弱（P〈0．01）。结论：川芎嗪可降低p38MAPK的活性，抑制TNF-α和IL-6的表达而发挥心肌保护作用。     

Puerarin reduces apoptosis in rat hippocampal neurons cultured in high glucose medium by modulating the p38 mitogen activated protein kinase and c-Jun N-terminal kinase signaling pathways

OBJECTIVE: To investigate the neuroprotective effect of puerarin on rat hippocampal neurons cultured in high glucose medium, and to examine the role of the p38 mitogen activated protein kinase(p38 MAPK) and c-Jun N-terminal kinase(JNK) signaling pathways in this effect.METHODS: Primary cultures of hippocampal neurons were prepared from newborn Sprague Dawley rats. Neuron-specific enolase immunocytochemistry was used to identify neurons. The neurons were cultured with normal medium(control group) or with high-glucose medium(high-glucose group),and puerarin(puerarin group), a p38 MAPK inhibitor(SB239063; p38 MAPK inhibitor group) or a JNK inhibitor(SP600125; JNK inhibitor group) were added. After 72 h of treatment, terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling assay was performed to detect apoptosis, and western blotting was used to assess protein levels of p-p38, p38, p-JNK and JNK.RESULTS: In the high-glucose group, the neuronal apoptosis rate and the p-p38/p38 and p-JNK/JNK ratios were higher than in the control group. The p38 MAPK and JNK inhibitors prevented this increase in the apoptosis rate. The apoptosis rates in the puerarin group, the p38 MAPK inhibitor group and the JNK inhibitor group were significantly decreased compared with the high-glucose group.Moreover, protein levels of p-p38 and p-JNK were significantly reduced, and the p-p38/p38 and p-JNK/JNK ratios were decreased in the puerarin group compared with the high-glucose group. In addition, compared with the high-glucose group,p-p38 levels and the p-p38/p38 ratio were reduced in the p38 MAPK inhibitor group, and p-JNK levels and the p-JNK/JNK ratio were decreased in the JNK inhibitor group.CONCLUSION: Puerarin attenuates neuronal apoptosis induced by high glucose by reducing the phosphorylation of p38 and JNK.     

Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke‐induced Gastric Epithelial–Mesenchymal Transition in Mice

Tobacco smoke (TS) has been shown to cause gastric cancer. Epithelial–mesenchymal transition (EMT) is a crucial pathophysiological process in cancer development. Mitogen‐activated protein kinase (MAPK) pathways play central roles in tumorigenesis including EMT process. Curcumin is a promising chemopreventive agent for several types of cancers. In the present study, we investigated the effects of TS on MAPK pathway activation and EMT alterations in the stomach of mice, and the preventive effect of curcumin was further examined. Results showed that exposure of mice to TS for 12 weeks resulted in activation of extracellular regulated protein kinases 1 and 2 (ERK1/2), the Jun N‐terminal kinase (JNK), p38, and ERK5 MAPK pathways as well as activator protein 1 (AP‐1) proteins in stomach. TS reduced the mRNA and protein expression levels of the epithelial markers E‐cadherin and ZO‐1, while the mRNA and protein expression levels of the mesenchymal markers vimentin and N‐cadherin were increased. Treatment of curcumin effectively abrogated TS‐triggered gastric activation of ERK1/2 and JNK MAPK pathways, AP‐1 proteins, and EMT alterations. These results suggest for the first time the protective effects of curcumin in long‐term TS exposure‐induced gastric MAPK activation and EMT, thus providing new insights into the pathogenesis and chemoprevention of TS‐associated gastric cancer. Copyright © 2015 John Wiley & Sons, Ltd.     

制大黄-川芎“药对”抑制造影剂肾病大鼠肾小管上皮细胞凋亡信号通路的机制研究

目的研究制大黄-川芎“药对”抑制造影剂。肾病（CIN）大鼠。肾小管上皮细胞凋亡信号通路的机制。方法将32只雄性sD大鼠分为正常组（A组）、模型组（B组）、药对组（C组）、N-乙酰半胱氨酸（NAC）组（D组）。C组于造模前7天每日灌胃“药对”水煎液,D组造模前3天每日腹腔注射NAC（150μg／g）。B、C、D3组按照文献方法制备CIN模型。造模后24h处死大鼠,测定血清肌酐（Scr）、尿素氮（BUN）;HE染色观察肾脏病理改变,Western印迹检测肾组织p-p38MAPK、Bcl-2及Bax表达。结果与A组比较,B、C、D组大鼠血清肌酐、尿素氮均明显升高（P〈0．05,P〈0．01）,出现肾间质水肿、肾小管上皮细胞胞浆空泡样变,p-p38MAPK、Bax蛋白表达上调,Bcl-2表达下降。与B组比较,C、D组血清肌酐、尿素氮明显降低（P〈0．05）,肾脏病理改变显著减轻,p-p38MAPK、Bax蛋白表达下降,而Bcl-2表达增加（P〈0．01）。结论p38MAPK通路活化参与了CIN大鼠急性。肾损伤过程,且制大黄-川芎“药对”能通过抑制该通路活化保护CIN大鼠肾功能。     

Effects of Curcumin on Tobacco Smoke‐induced Hepatic MAPK Pathway Activation and Epithelial–Mesenchymal Transition In Vivo

Tobacco smoke is a major risk factor for hepatic cancer. Epithelial–mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen‐activated protein kinase (MAPK) pathways play important roles in tobacco smoke‐associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice. Our results indicated that exposure of mice to tobacco smoke for 12 weeks led to activation of ERK1/2, JNK, p38 and ERK5 pathways as well as activator protein‐1 (AP‐1) proteins in liver tissue. Exposure of mice to tobacco smoke reduced the hepatic mRNA and protein expression of the epithelial markers, while the hepatic mRNA and protein levels of the mesenchymal markers were increased. Treatment of curcumin effectively attenuated tobacco smoke‐induced activation of ERK1/2 and JNK MAPK pathways, AP‐1 proteins and EMT alterations in the mice liver. Our data suggested the protective effect of curcumin in tobacco smoke‐triggered MAPK pathway activation and EMT in the liver of BALB/c mice, thus providing new insights into the chemoprevention of tobacco smoke‐associated hepatic cancer. Copyright © 2017 John Wiley & Sons, Ltd.     

电针药氧对大鼠全脑缺血再灌注后Bcl-2、Bax蛋白表达的影响

目的:探讨电针药氧对大鼠全脑缺血再灌注后海马CA1区Bcl-2、Bax蛋白表达的影响。方法:采用改良Pulsinelli4血管阻断全脑缺血方法,建立短暂反复全脑缺血再灌注(Cerebral ischemia/reperfu-sion,CI/R)大鼠模型。选择造模成功的大鼠随机分为5组:假手术组(S组)、模型组(M组)、电针组(E组)、药氧组(O组)、电针药氧联合组(C组),每组6只大鼠。采用免疫组化与医学图像分析检测大鼠海马CA1区Bcl-2、Bax蛋白阳性细胞数目、平均灰度。结果:M组与S组比较,海马CA1区Bcl-2、Bax蛋白阳性细胞数目均增多,平均灰度均降低(P0.05;P0.01);E、O、C组与M组比较,Bcl-2蛋白阳性细胞数目增多,平均灰度降低,Bax蛋白阳性细胞数目减少,平均灰度升高(P0.05),以C组效果更明显。结论:全脑缺血后早期电针药氧可上调Bcl-2、下调Bax蛋白的表达,这可能是电针药氧治疗缺血性脑血管病的机制之一。     

Huangkui capsule,an extract from Abelmoschus manihot (L.) medic,ameliorates adriamycin-induced renal inflammation and glomerular injury via inhibiting p38MAPK signaling pathway activity in rats

Ethnopharmacological relevance

Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases in China. Huangkui capsule (HKC), an extract from AM, has been proved clinically effective in improving renal inflammation and glomerular injury in chronic kidney disease (CKD). However, the dose-effects and the mechanisms involved in vivo are still unclear.

Aim of the study

This study was performed to examine the dose-effects of HKC on renal inflammation and glomerular lesion in adriamycin-induced nephropathy (ADRN), then to clarify the mechanisms in vivo of HKC by investigating its actions on modulating the activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway.

Materials and methods

The rats with chronic ADRN, created by the unilateral nephrectomy and twice adriamycin injections (ADR, 4 mg/kg and 2 mg/kg) within 4 weeks, were divided into four groups, a Sham group, a Vehicle group, a high-dose HKC group, and a low-dose HKC group, and that, sacrificed at the end of the 4th week after the administration. The rat's general status, renal morphological appearance, proteinuria, blood biochemical parameters, glomerular morphological changes, podocyte shape, and macrophage (ED1⁺ and ED3⁺ cells) infiltration in glomeruli were examined, respectively. The protein expressions of inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-2, as well as p38MAPK signaling molecules such as transforming growth factor (TGF)-β1, p38MAPK, and phosphorylated-p38MAPK (p-p38MAPK), were also evaluated individually.

Results

HKC at high dose of 2 g/kg/d not only significantly ameliorated the rat's general status, renal morphological appearance, proteinuria, albumin, and glomerulosclerosis, but also obviously reduced the infiltrated ED1⁺ and ED3⁺ macrophages in glomeruli and TNF-α protein expression in the kidney, in addition to these, evidently down-regulated TGF-β1 and p-p38MAPK protein expressions in ADRN rats, but had no influence on podocyte shape and renal function.

Conclusion

HKC could dose-dependently ameliorate renal inflammation and glomerular injury in ADRN rats, by way of reducing the infiltration and the activation of macrophages in glomeruli, and TNF-α protein expression in the kidney, as well as inhibiting p38MAPK signaling pathway activity via the down-regulation of p-p38MAPK and TGF-β1 protein expressions in vivo.     

参附注射液对缺血性脑卒中大鼠血脑屏障的影响

目的:探讨参附注射液对局灶性脑缺血大鼠血脑屏障(blood brain barrier,BBB)的影响及其机制。方法:利用线栓法制作脑缺血/再灌注模型,再灌注24h后进行神经功能评分,应用伊文思蓝法(Evans Blue,EB)观察对照组与参附注射液治疗组(SFI)BBB通透性,采用干湿重法比较脑含水量、TTC法比较脑梗死面积。蛋白印迹法检测金属硫蛋白酶9(matrix metalloproteinase-9,MMP-9)及细胞外调节蛋白激酶(Extracellular regulated protein kinases,ERK)的表达。结果:参附注射液治疗组的血脑屏障通透性、脑含水量、脑梗塞体积、神经功能缺损程度均比对照组明显降低(P0.05)。和对照组相比,SFI组的MMP-9及磷酸化ERK的蛋白表达明显降低。结论:参附注射液对大鼠脑缺血模型的血脑屏障具有保护作用,其作用机制与抑制MMP-9及ERK信号通路相关。     

中风膏抗脑缺血再灌注损伤的实验研究

目的:观察中风膏对脑缺血再灌注损伤的神经保护作用。方法:采用线栓法建立大鼠大脑中动脉栓塞(MCAO)模型。实验分为假手术组、模型组、中风膏小剂量、大剂量组,分组给药7天后造模,观察中风膏对大鼠脑缺血再灌注后神经功能缺损评分、脑梗死体积、脑组织结构及神经元形态的影响。结果:各组出现了不同程度的神经功能缺损症状,与模型组比较,再灌注24小时后给药组可明显改善大鼠神经缺损症状(P0.05);再灌注24小时后给药组梗死体积小于模型组(P0.05);脑缺血再灌注24小时后模型组缺血侧皮质区组织结构及细胞形态失常,而给药组脑组织结构及神经元形态受损程度较轻。结论:中风膏对大鼠脑缺血再灌注损伤有神经保护作用。