粉防己碱对糖尿病大鼠心肌保护作用及机制的研究

目的研究粉防己碱对糖尿病(DM)大鼠心肌的保护作用及相关机制。方法36只W istar大鼠用链脲佐菌素(STZ)诱发糖尿病模型后,随机分为粉防己碱治疗组、苯那普利治疗组及糖尿病未治疗组,以10只正常大鼠作为对照。12 w末检测血糖、血脂、心肌组织血管紧张素Ⅱ,应用RT-PCR检测心肌结缔组织生长因子(connective tissue growth factor,CTGR)mRNA的表达水平。结果DM未治疗组心肌组织血管紧张素Ⅱ含量、CTGR mRNA的表达分别为(26.5±3.38)和(1.0±0.10),明显高于对照组和治疗组(P<0.01)。结论粉防己碱能在一定程度上降低心肌血管紧张素Ⅱ含量,抑制CTGF mRNA表达,从而可能减轻糖尿病性心肌病的病理变化。     

Nanoparticle-mediated local delivery of pioglitazone attenuates bleomycin-induced skin fibrosis

Background

Nanoparticle-loaded delivery systems have attracted much attention recently. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful biodegradable polymers for biomedical applications. There are only a few studies on the treatment of dermal fibrosis with sustained-release drugs. Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in endogenous anti-fibrotic defense mechanisms. Recent studies have suggested that pioglitazone, a synthetic PPAR-γ activator, has effects beyond reducing blood sugar and it can reduce fibrosis and inflammation when used systemically.

辛伐他汀对慢性心衰大鼠心肌纤维化及TGF-β1 CTGF表达的影响

目的探讨结缔组织生长因子(CTGF)在慢性心衰大鼠心肌纤维化(myocard ial fibrosis,MF)发生发展中的作用,以及辛伐他汀改善慢性心衰时心室重构和MF可能的作用机制。方法30只雄性W istar大鼠随机分为三组,假手术组(sham组)8只,模型组(model组)及辛伐他汀组(simvastatin组),每组11只。采用腹主动脉缩窄法制作慢性心衰模型,喂养8周后simvastatin组大鼠予以辛伐他汀2mg/(kg.d)灌胃,model组用生理盐水灌胃。8周后检测血流动力学参数,用MASSON染色法观察左室心肌胶原形态,图像分析测量胶原容积分数(CVF)和血管周围胶原面积(PVCA),免疫组化法检测心室肌中TGF-β1、CTGF表达。结果①CVF、PVCA在model组大鼠明显高于sham组大鼠(P<0.01);与model组比较,simvastatin组则显著降低(P<0.01)。②TGF-β1、CTGF在sham组表达较弱,model组表达增强,simvastatin组则减弱。结论辛伐他汀明显改善心室重构和MF,改善心功能,此作用可能与影响CTGF表达有关。     

Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases

Connective tissue growth factor (CTGF), a multifunctional protein of the CCN family, regulates cell proliferation, differentiation, adhesion, and a variety of other biological processes. It is involved in the disease-related pathways such as the Hippo pathway, p53 and nuclear factor kappa-B (NF-κB) pathways and thus contributes to the developments of inflammation, fibrosis, cancer and other diseases as a downstream effector. Therefore, CTGF might be a potential therapeutic target for treating various diseases. In recent years, the research on the potential of CTGF in the treatment of diseases has also been paid more attention. Several drugs targeting CTGF (monoclonal antibodies FG3149 and FG3019) are being assessed by clinical or preclinical trials and have shown promising outcomes. In this review, the cellular events regulated by CTGF, and the relationships between CTGF and pathogenesis of diseases are systematically summarized. In addition, we highlight the current researches, focusing on the preclinical and clinical trials concerned with CTGF as the therapeutic target.     

排毒保肾汤含药血清对TGF-β1刺激的肾小管上皮细胞表达α-SMA及CTGF的影响

目的观察排毒保肾汤含药血清对转化生长因子β1(TGF-β1)刺激的人肾小管上皮细胞(HKC)表达α-平滑肌肌动蛋白(α-SMA)及结缔组织生长因子(CTGF)的影响。方法给予家兔中药煎剂灌胃7d后,制备兔含药血清,采用不同浓度的兔含药血清处理经10ng/mLTGF-β1诱导活化的HKC,RT-PCR法测定其α-SMAmRNA、免疫组化法检测CTGF蛋白水平的变化。结果兔含药血清作用于HKC48h后,呈剂量依赖方式逆转HKC表达α-SMAmRNA及CTGF蛋白水平。结论排毒保肾汤含药血清发挥阻抑肾间质纤维化的作用可能与抑制肾小管上皮细胞-肌成纤维细胞转分化有关。