辛伐他汀调节p38和CARP与改善心肌重塑的关系

 目的探讨p38丝裂原激活的蛋白激酶(p38MAPK,p38)和心锚重复蛋白(cardiac ankyrin repeat protein,CARP)与心肌梗死后心肌重塑的关系,及辛伐他汀改善心肌梗死后心肌重塑的机制。方法结扎大鼠冠脉前降支致心肌梗死,术后24h存活大鼠随机分为心肌梗死组(MI组)、p38抑制剂SB203580组(SB组)、辛伐他汀组(Sim组)和假手术组(sham组)。7d后测定左心室重量指数(LVWI),心肌细胞横切面面积(CSA),RT-PCR和免疫组化法测定p38和CARP在非梗死区心肌中的表达。结果与Sham组相比,MI组LVWI和CSA明显增加(P<0.01),磷酸化p38(P-p38)和CARP表达明显增加(P<0.05)。与MI组相比,SB组和Sim组LVWI和CSA明显降低(P<0.01),SB组CARP表达低于MI组(P<0.01),Sim组p38和CARP表达明显低于MI组(P<0.01)。结论大鼠心肌梗死后p38和CARP表达增加;抑制p38可抑制CARP的表达,CARP可能部分受p38信号通路调节;辛伐他汀改善心肌梗死后心肌重塑的作用可能与抑制p38和CARP有关。     

Effect of traditional Chinese medicine Shu-mai-tang on angiogenesis, arteriogenesis and cardiac function in rats with myocardial ischemia

Ischemic heart disease is one of the leading causes of morbidity and mortality worldwide. Shu-mai-tang (SMT) is a traditional Chinese medicine for the treatment of ischemic heart disease. To better understand the underlying cardioprotection mechanisms of SMT on myocardial ischemia (MI), the effect of SMT on angiogenesis, arteriogenesis and cardiac function was investigated in a rat model of MI, as well as the potential mechanism. Rats with a ligated left anterior descending coronary artery (MI model) were randomized (24 rats/group) to receive SMT/LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor], SMT or no treatment. A sham-operation group was included. It was demonstrated that 2 and 4 weeks after treatment the oral administration of SMT significantly increased capillaries and arterioles, suppressed myocardial fibrosis, as well as significantly increased cardiac phosphorylation of Akt, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-BB) levels and functional improvement. PI3K inhibitor down-regulated SMT-induced angiogenesis and arteriogenesis. These novel therapeutic properties of SMT to induce the reconstitution of stable blood supply networks, reverse LV remodeling may offer an alternative therapy for the treatment of ischemic heart disease. The potential mechanism may be that SMT promotes VEGF and PDGF-BB-mediated angiogenesis and arteriogenesis through the PI3K/Akt signaling pathway.     

丝裂原活化蛋白激酶/细胞外信号调节激酶信号通路在穿心莲内酯治疗心肌缺血/再灌注损伤大鼠中的分子机制

目的:从丝裂原活化蛋白激酶/细胞外信号调节激酶(MAPK/ERK1/2)信号通路研究穿心莲内酯(AG)对心肌缺血/再灌注损伤(MI/RI)大鼠的分子机制,为AG能够安全地用于MI/RI的预防提供参考.方法:雄性SPF级SD大鼠60只,购入后先全部予适应性喂养2周,后将其随机分为假手术组、模型组、银杏内酯B干预组,AG治...     

电针“内关”对心肌肥厚模型大鼠p38丝裂原激活蛋白激酶信号通路的影响

目的:探讨电针“内关”穴治疗心肌肥厚的作用机制.方法:SD大鼠40只用随机数字表法分为正常组、模型组、模型+p38抑制剂组、模型十电针组,每组10只.采用皮下注射盐酸异丙肾上腺素3 mg/(kg·d)建立心肌肥厚大鼠模型,模型+p38抑制剂组在造模基础上每日皮下注射0.3 mg/kg p38丝裂原激活蛋白激酶(p38 MAPK)特异性抑制剂SB 203580;模型十电针组电针“内关”穴,采用连续波,频率2 Hz,强度1 mA,通电20 min,1次/d,共14 d.其他两组不予治疗干预.放射免疫法技术检测心肌组织肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)含量,免疫印迹法检测p38MAPK、磷酸化p38 MAPK(p-p38 MAPK)含量.观察电针“内关”穴对TNF-α和IL-1β、p38 MAPK、p-p38 MAPK的影响.结果:与正常组大鼠比较,模型组大鼠TNF-α和IL-1β、p38 MAPK、p-p38 MAPK均显著升高(均P＜0.01);经抑制剂和电针处理后,模型+p38抑制剂组和模型十电针组大鼠TNF-α、IL-1β、p38 MAPK、p-p38 MAPK均明显降低,与模型组比较差异有统计学意义(均P＜0.05),与正常组比较差异亦有统计学意义(P＜0.05,P＜0.01);模型+p38抑制剂组和模型十电针组之间比较差异无统计学意义(P＞0.05).结论:电针“内关”可以明显抑制心肌肥厚p38 MAPK的磷酸化,这种保护作用可能通过抑制TNF-α、IL-1β等炎性因子的表达实现对p38 MAPK信号通路调节.     

Protection of Shengmai Recipe on Improving Cardiac Function and Attenuating Kidney Injury in Pressure Overload Rats

Objective Shengmai Recipe (SMR) is a Chinese patent medicine used for the treatment of chronic heart disease. In order to further assess the renal-protective effect against ischemia lesion of SMR, the cardioprotective effect of SMR on pressure overload-induced left ventricular (LV) systolic dysfunction and the potential mechanism on alleviating myocardial damage, myocardial fibrosis, and renal ischemia lesion in chronic heart failure (CHF) rats were investigated. Methods Rats with partially ligated abdominal aorta were randomly divided into model, Sham, and SMR groups. One week after recovery from surgery, animals were preventively ig administered with SMR at the dose of 810 mg/kg once daily for 8 weeks. Cardiac function and structure, endogenous biomarkers (CK-MB and LDH), myocardial fibrosis, and organ pathological change were estimated by echocardiography, immunodepression and velocity method, hematoxylin- eosin staining, and masson’s trichrome staining, respectively. Results The administration of SMR significantly decreased serum CK-MB and LDH levels and reduced myocardial fibrosis. Interestingly, SMR not only improved cardiac function but also ameliorated kidney injury induced by ischemia in CHF rats. Conclusion SMR could enhance the LV contractile function, reduce myocardial necrosis, and reverse LV remodeling in CHF rats, and most importantly, SMR could be used to treat the renal ischemia injury in pressure overload rats.     

益心附葶饮对主动脉缩窄大鼠心肌纤维化及p38MAPK/NF-κB p65信号通路的影响

目的:研究益心附葶饮对腹主动脉缩窄致心力衰竭大鼠心肌纤维化的改善作用及机制.方法:采用腹主动脉缩窄法构建心衰大鼠模型,将造模成功的30只大鼠随机分为模型组和中药组,另设15只穿线不结扎的假手术组.中药组给予益心附葶饮灌胃3.5 g/(kg·d),假手术组和模型组给予等体积蒸馏水灌胃.喂养8周后取材,采用Masson染色...     

黄芪对肝纤维化大鼠肝损伤保护作用及机制研究

目的:研究黄芪对肝纤维化大鼠肝损伤的保护作用及相关机制。方法:将SD大鼠随机分为正常对照组、肝纤维化模型组、黄芪后处理组和阳性对照组,检测各组大鼠血清中ALT、AST活性和TBIL水平变化; 逆转录-聚合酶链反应检测各组大鼠肝脏组织5种主要致纤维化因子p38MAPK、TGF -β1、α-SMA、CTGF和Collegen Ⅳ mRNA表达水平; 免疫印迹法检测p38MAPK信号通路上下游蛋白MKK3和ATF-2的表达变化。结果:与肝纤维化模型组比较,黄芪后处理组大鼠血清中ALT、AST和TBIL水平明显降低(P<0.05),肝纤维病理变化明显减轻,p38MAPK、MKK3和ATF-2蛋白表达量均降低(P<0.05)。结论:黄芪通过p38MAPK信号通路对实验性肝纤维化大鼠肝损伤具有效的保护作用。     

Effects of Tribuli saponins on ventricular remodeling after myocardial infarction in hyperlipidemic rats

This experiment was designed to determine whether Tribuli saponins (TS) relieve left ventricular remodeling (VR) after myocardial infarction (MI) in a murine hyperlipemia (HL) model. MI and HL models were induced and high and low doses of TS and simvastatin were administrated to the rats. Four weeks later, echocardiographic observation was performed and the left and right ventricular weight index (LVWI, RVWI) was calculated. Echocardiographic results showed that both high dose of TS and simvastatin had a beneficial effect on increasing fractional shortening (FS) and ejection fraction (EF), reducing left ventricular end diastolic volume (LVEDV), systolic volume (LVESV), left ventricular dimension end diastole (LVDd) and systole (LVDs), and decreasing LVWI, as compared to those in the HL-MI model group (p < 0.05, 0.01). Both medicines had little impact on thickness of the anterior and posterior wall. No significant difference was observed between each treatment group (p > 0.05). In conclusion, TS not only lowered serum lipidemia, but also relieved left ventricular remodeling, and improved cardiac function in the early stage after MI.     

麝香通心滴丸通过促血管新生改善糖尿病合并心肌梗死大鼠心功能的作用机制研究

[目的] 从促进血管新生角度探究麝香通心滴丸对糖尿病合并心肌梗死大鼠心功能的保护效果和作用机制。[方法] 通过腹腔注射链脲佐菌素（55 mg/kg）及冠状动脉左前降支结扎术建立糖尿病合并心肌梗死大鼠模型,随机将大鼠分为糖尿病合并心肌梗死组（MI组）、麝香通心滴组（STDP组）[20 mg（/kg· d）],并设立正常血糖假手术组（Sham组）,每组6只。STDP组每日予药物灌胃,Sham组与MI组每日予同体积蒸馏水。观察大鼠体质量、空腹血糖变化,给药28 d后采用超声心动图检测心功能;病理检测采用苏木精-伊红（HE）与Masson染色观察心肌结构及纤维化病变情况;免疫荧光麦胚凝集素（WGA）染色测量心肌细胞面积;免疫组化法观察心肌血小板-内皮细胞黏附分子-1（CD31）表达情况并测定心肌毛细血管密度;Wes全自动蛋白质印迹定量分析法、蛋白免疫印迹法（Western blot）测定心脏组织中血管内皮生长因子（VEGF）、磷酸化血管内皮生长因子受体2（p-VEGFR2）、促血管生成素-1（Ang-1）、酪氨酸激酶受体-2（Tie-2）、内皮型一氧化氮合酶（eNOS）、诱导型一氧化氮合酶（iNOS）、磷酸化内皮型一氧化氮合酶（p-eNOS）的蛋白表达水平。[结果] 糖尿病大鼠出现明显的多饮多食多尿现象,血糖显著升高;与Sham组比较,MI组大鼠的左心室射血分数和短轴缩短率比值明显降低,心脏微血管密度明显下降,并出现明显的心肌纤维化与心肌细胞肥大（P＜0.01）;同时心肌组织中VEGF、p-VEGFR2、Ang-1、Tie-2、eNOS、p-eNOS蛋白表达明显降低（P＜0.01）,iNOS表达水平显著增加（P＜0.01）。与MI组相比,STDP组大鼠心肌纤维化和心肌细胞肥大明显改善,微血管密度增加,VEGF、p-VEGFR2、Ang-1、Tie-2、eNOS、p-eNOS的蛋白表达水平提高（P＜0.01或P＜0.05）,iNOS蛋白表达降低（P＜0.05）,心功能明显改善。[结论] 麝香通心滴丸可保护糖尿病合并心肌梗死大鼠心功能,其作用机制可能与促进血管新生、改善心肌微循环障碍有关。     

电针经p38 MAPK信号通路对坐骨神经损伤大鼠脊髓中AQP1和AQP4表达的影响＊

目的 探讨电针（electroacupuncture，EA）治疗对坐骨神经损伤大鼠脊髓中水通道蛋白AQP1和AQP4表达的影响，并揭示其可能作用机制。方法 将60只SD大鼠随机分成假手术组（Sham组）、模型组（Model组）、电针组（EA组）、抑制剂组（SB203580组）和电针 + 抑制剂组（EA + SB203580组），每组12只。采用钳夹法复制坐骨神经损伤大鼠模型，并给予电针和p38抑制剂SB203580干预14天。分别于干预前及干预后第7天和14天检测坐骨神经功能指数（SFI）；HE染色观察损伤处远端坐骨神经组织病理学变化；BL-410电生理系统检测大鼠神经传导速度（NCV）；qRT-PCR检测脊髓AQP1和AQP4 mRNA表达水平；Western blot检测脊髓AQP1、AQP4、p-p38MAPK和p38MAPK蛋白表达水平。结果 与Sham组比较，Model组大鼠坐骨神经组织结构不完整，出现明显炎症浸润和病理损伤，EA组和SB203580组大鼠坐骨神经组织相较于Model组坐骨神经组织炎症浸润和病理损伤得到明显缓解，EA + SB203580组与SB203580组的差异不大。与Sham比较，Model组大鼠脊髓中AQP1和AQP4 mRNA和蛋白表达水平以及p-p38MAPK/p38MAPK蛋白比值均显著增加，而SFI值和NCV显著降低（P < 0.01）；与Model组比较，EA组和SB203580组大鼠脊髓中AQP1 和AQP4 mRNA和蛋白表达水平、p-p38MAPK/p38MAPK蛋白比值均显著降低，而SFI值和NCV显著升高（P < 0.01）；与SB203580组比较，EA + SB203580组检测指标无显著性变化（P > 0.05）。结论 电针刺激可抑制脊髓中AQP1和AQP4表达，改善大鼠坐骨神经损伤，其可能与抑制p38MAPK信号通路活化有关。     

川芎嗪对心肌缺血再灌注损伤大鼠HSP25和p38MAPK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只健康成年Wistar大鼠被随机分为3组:假手术(sham)组、缺血再灌注损伤(IR)组、川芎嗪预处理组(LI).建立心肌缺血再灌注损伤大鼠模型,应用免疫组化S-P法,检测HSP25和p38MAPK蛋白的表达.结果:LI组与IR组比较,HSP25蛋白阳性表达显著增强(P<0.01),p38MAPK蛋白阳性表达显著减弱(P<0.01),在LI组二者呈负相关.结论:川芎嗪可增强HSP25蛋白表达、降低p38MAPK的活性,抑制炎症反应从而发挥心肌保护作用.     

补肾活血复方含药血清对大鼠成骨细胞磷酸化GSK-3β、p38MAPK及ERK1/2蛋白的影响

目的:观察补肾活血复方含药血清对大鼠成骨细胞磷酸化糖原合成激酶3β(GSK-3β)、p38丝裂原活化蛋白激酶(p38 MAPK)及细胞外信号调节激酶1/2(ERK1/2)蛋白的作用。方法:3月龄SD雌性大鼠灌胃制备空白血清和含药血清,并分离培养1日龄新生鼠颅骨成骨细胞。实验分为空白血清组和含药血清组,分别采用MTT、ELISA、Western-blot等方法检测两组成骨细胞的增殖、ALP和BGP的分泌及磷酸化GSK-3β、p38 MAPK和ERK1/2蛋白的变化。结果:与空白血清组相比,含药血清组可明显促进成骨细胞的增殖、ALP和BGP的分泌,并促进胞内磷酸化p38 MAPK和ERK1/2蛋白的表达,对磷酸化GSK-3β蛋白的表达未见明显影响。结论:补肾活血复方含药血清可促进大鼠成骨细胞的增殖和分化,提高p38 MAPK和ERK1/2蛋白磷酸化水平。     

心复康对心肌梗死大鼠心室重塑和功能的影响

[目的]观察中药心复康对大鼠心肌梗死心室重塑参数和心功能的影响,探讨中药对心室重塑的保护作用。[方法]采用冠状动脉结扎法制作心肌梗死模型,术后随机分为假手术组、模型组、中药高剂量组和中剂量组,每组12只。中药高剂量(每天81g/kg)和中剂量组(每天40.5g/kg)给予中药心复康水煎剂灌胃,假手术组和模型组每天等量生理盐水灌胃。28d后,处死动物之前行心脏超声心动图观察心脏功能;称量体质量;称量肺的相对质量;病理切片观察心脏微观结构改变。[结果]中药高剂量组左室舒张末期内径(LVDd),左室收缩末期内径(LVDs),舒张末期室间隔厚度(IVSd),收缩末期室间隔厚度(IVSs),舒张末期左室后壁厚度(LVPWd),收缩末期左室后壁厚度(LVPWs),射血分数(EF),每分钟排出量(CO),左室短轴缩短率(FS),与模型组比较均有统计学意义。模型组与各组比较胶原纤维增多,排列紊乱。[结论]中药可以改善心室重塑大鼠的心功能,保护心脏结构重整;抑制心脏胶原纤维的增生。     

压力超负荷大鼠心肌血红素加氧酶-1表达与氧化应激水平的相关性

目的:探讨压力超负荷大鼠心肌血红素加氧酶-1(HO-1)表达水平与心肌氧化应激水平的关系。方法:将40只SD大鼠随机抽取8只作为假手术组(Sham组),其余32只大鼠采用腹主动脉缩窄术制备压力负荷模型,将术后存活的22只大鼠随机分为模型组(Model组,n=7)、丹参酮ⅡA组(TanⅡA组,n=7)及丹参酮ⅡA+HO-1抑制剂组(TanⅡA+Zn PP组,n=8)。术后4周造模成功并开始给药,疗程为4周。8周后检测心脏质量指数、左心室质量指数,观察心肌组织HE染色,比色法检测心肌氧化应激水平,Western blotting法检测心肌HO-1的蛋白表达水平。结果:1)与Sham组比较,Model组大鼠心脏质量指数和左心脏质量指数明显升高(P0.01);与Model组比较,TanⅡA组和TanⅡA+Zn PP组心脏质量指数和左心脏质量指数均有不同程度下降,而TanⅡA组下降更为显著(P0.01)。2)HE染色结果显示,与Sham组比较,Model组大鼠心肌纤维化程度加重;与Model组相比,TanⅡA组和TanⅡA+Zn PP组心肌组织形态学均有不同程度的改善,而TanⅡA组改善更为明显。3)TanⅡA组血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平高于Model组和TanⅡA+Zn PP组(P0.01),MDA水平低于Model组和TanⅡA+Zn PP组(P0.01)。4)TanⅡA组心肌HO-1的蛋白表达水平高于其余3组(P0.01)。结论:丹参酮ⅡA可以提高心肌HO-1表达水平,增强压力负荷大鼠心肌抗氧化能力,减缓心室重构进程。     

扶正化瘀胶囊对心肌梗死大鼠心脏结构和功能的影响1）

目的 探讨扶正化瘀胶囊对心肌梗死（MI）大鼠心脏结构和功能的影响.方法 大鼠随机分为模型组、扶正化瘀胶囊组、盐酸法舒地尔组和假手术组,每组8只.结扎左冠状动脉前降支制作MI大鼠模型,假手术组只穿线,不结扎.术后给予相应药物治疗4周,假手术组和模型组给予去离子水.治疗4周后采用超声心动图检查评价大鼠心脏结构和功能的变化.结果 模型组左室射血分数（LVEF）、左室短轴缩短分数（LVFS）、室间隔收缩末期厚度（IVSTs）低于假手术组,左心室舒张末期内径（LVDd）、左心室收缩末期内径（LVDs）高于假手术组（P＜0.01）;盐酸法舒地尔组LVDs低于模型组,LVEF、LVFS均高于模型组,两组比较具有统计学意义（P〈0.05）;扶正化瘀胶囊组IVSTs、LVEF、LVFS均高于模型组,LVDd、LVDs低于模型组（P＜0.05）.结论 抗纤维化中药扶正化瘀胶囊可改善MI大鼠左室重构并能提高心功能.     

Protocatechuic acid attenuates angiotensin II‐induced cardiac fibrosis in cardiac fibroblasts through inhibiting the NOX4/ROS/p38 signaling pathway

Cardiac fibrosis plays a crucial role in the pathogenesis of myocardial infarction (MI). It has been found that differentiation of cardiac fibroblasts (CFs) into myofibroblasts is a major event in the process of cardiac fibrosis. In the present study, we aimed to investigate the effects of protocatechuic acid (PCA), a cardiac protective agent, on the CFs differentiation in vitro. The results showed that PCA exhibited inhibitory effects on the cell proliferation and migration in angiotensin II (Ang II)‐induced CFs. PCA treatment suppressed the Ang II‐induced expression of α‐smooth muscle actin (α‐SMA), which is a hallmark of myofibroblasts. In addition, the production of extracellular matrix (ECM) proteins, including type I collagen (Col I) and connective tissue growth factor (CTGF), were significantly decreased in the PCA‐treated CFs. The Ang II‐induced increased levels of matrix metalloproteinase (MMP)‐2, and MMP‐9 were reduced by PCA. Furthermore, PCA resulted in decrease in reactive oxygen species (ROS) generation, as well as the expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme 4 (NOX4) and p‐p38 in Ang II‐induced CFs. These findings showed that PCA treatment prevented the Ang II‐induced cardiac fibrosis by inhibiting the NOX4/ROS/p38 signaling pathway in vitro, suggesting that PCA might be a therapeutic agent for MI.     

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.     

丹参提取物对系膜增生性肾小球肾炎大鼠TGF-β1/p38MAPK信号通路的影响研究

目的:观察丹参提取物对系膜增生性肾小球肾炎(Mesangial proliferative glomerulonephritis,MsPGN)大鼠肾组织转化因子-β1(Transforming growth factor-β1,TGF-β1)和p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)的影响。方法:将46只SD大鼠分为正常组、缬沙坦组、模型组、丹参提取物组,除正常组外,其余各组大鼠建立MsPGN模型。丹参提取物组按丹参5 g/(kg·d)的剂量灌胃给药;缬沙坦组按缬沙坦0.01 g/(kg·d)的剂量溶于温水灌胃,模型组和正常组每天给予等量温水灌胃,连续灌胃12周后处死大鼠。Western blot检测大鼠肾组织TGF-β1和p38 MAPK蛋白的表达,RT-PCR检测TGF-β1和p38MAPK的mRNA表达。结果:与正常组比较,模型组大鼠24 h尿蛋白水平、TGF-β1和p38MAPK蛋白相对表达量及mRNA表达均显著升高(P<0.05);与模型组比较,给药6周和12周缬沙坦组、丹参提取物组24 h尿蛋白水平显著降低(P<0.05);TGF-β1和p38MAPK蛋白相对表达量及mRNA表达均显著下降(P<0.05);与缬沙坦组比较,丹参提取物组TGF-β1和p38MAPK mRNA表达均下降(P<0.05)。结论:丹参提取物的肾保护作用可能是通过下调TGF-β1、p38MAPK蛋白和mRNA水平,抑制TGF-β1/p38MAPK信号通路激活来实现的。     

银杏苦内酯B对重症急性胰腺炎大鼠p38丝裂原活化蛋白激酶活性的影响

目的观察银杏苦内酯B(BN52021)对重症急性胰腺炎(SAP)大鼠胰腺组织p38丝裂原活化蛋白激酶(p38MAPK)活性的影响。方法Wistar雄性大鼠随机分为阴性对照组(NC组)、SAP模型组(SAP组)、BN52021治疗组(BN组),每组按术后不同时相点(1、2、3、6、12、24h)分为6小组,用Western blotting法分别检测胰腺组织p38MAPK表达与激活情况,同时对胰腺组织进行病理学观察和测定血清淀粉酶活性的变化。结果血清淀粉酶和病理学结果显示SAP造模成功,BN52021能降低SAP大鼠的血清淀粉酶活性,病理学评分在3、6、12h较SAP组显著降低(P<0.05);NC组在各时相点均只检测到少量磷酸化的p38MAPK,SAP组和BN组在各时相点均较NC组显著升高(P<0.05),BN组在6、12、24h较SAP组显著降低(P<0.05)。结论BN52021可部分抑制SAP大鼠胰腺组织p38MAPK的活化,从而发挥其治疗作用。     

麝香保心丸对肝硬化大鼠心肌重构的抑制作用及其机制

目的 研究麝香保心丸对大鼠肝硬化致心肌重构的抑制作用及其机制.方法 随机选取70只SD大鼠,每周给药CCl4橄榄油溶液2次(周1和周4各1次),连续给药8周,制各肝纤维化模型.造模第2周末随机处死10只,取肝组织进行HE染色以观察肝纤维化程度,其余60只模型大鼠随机均分为贝那普利(10 mg/kg)阳性对照组、麝香保心丸(45 mg/kg)组和模型组,造模同时给药,每天1次,连续给药6周.另取10只大鼠作为对照组.造模第8周末,测量各组大鼠血压;检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平;Masson染色法检测肝脏与心肌组织中胶原的量;Western blotting检测基质金属蛋白酶-9 (MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)蛋白的表达;ELISA法检测心肌组织中羟脯氨酸、Ⅰ型和Ⅲ型胶原的量;观察各组大鼠肝功能以及肝脏纤维化病变,分析大鼠左心室心肌肥厚指数(LVHI).结果 模型组大鼠肝功能不同程度地损害、肝纤维化及心肌损伤.与模型组相比,麝香保心丸组大鼠血清ALT、AST及肝脏胶原的量明显下降(P＜0.01),心肌组织中MMP-9、TIMP-1的表达下调,羟脯氨酸、Ⅰ型和Ⅲ型胶原、蓝染胶原的量和LVHI均明显降低(P＜0.05),MMP-9/TIMP-1值升高(P＜0.05).贝那普利对各项指标也有不同程度的改善作用.结论 麝香保心丸在抗肝纤维化、改善心肌重构方面的疗效与贝那普利无显著差异,其对肝损害的肝保护作用强于贝那普利且对血压无明显影响,整体疗效优于贝那普利.