共查询到20条相似文献,搜索用时 15 毫秒
1.
Liver fibrosis is considered to be a result of chronic liver pathological changes, and hepatic stellate cells (HSCs) play an important role during this process. Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities. This study focused on the effects of evodiamine on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and HSCs in vitro via the TGF-β1/Smad signaling pathway. A liver fibrosis rat model was established by the intraperitoneal injection of CCl4 (3 ml/kg, 30% in olive oil). Evodiamine (15 and 25 mg/kg) was administered orally for 8 weeks. HSCs were treated with different evodiamine concentrations. The results indicated that evodiamine could improve the histopathological abnormalities in liver tissues and decrease the level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hydroxyproline, and total bilirubin (TBIL). Concentrations of IL-6, tumor necrosis factor-α (TNF-α), collagen-I (COL-I), and collagen-III (COL-III) were reduced by evodiamine. Western blotting and real-time PCR showed that protein expression of transforming growth factor-β (TGF-β1), p-Smad 2/3 (phosphorylation of Smad 2/3), and smooth muscle alpha-actin (α-SMA) as well as mRNA expression of TGF-β1 and α-SMA in liver tissues were downregulated by evodiamine. The cell proliferation, production of hydroxyproline, and the protein expression of TGF-β1, p-Smad 2/3, and α-SMA in HSCs were dose-dependently reduced by evodiamine. Collectively, evodiamine had an antifibrosis effect in CCl4-induced liver fibrosis, and reduced HSCs proliferation and collagen metabolism in vitro. The major mechanism was downregulation of relative expression of TGF-β1, p-Smad 2/3, and α-SMA. 相似文献
2.
目的 观察黄芪甲苷对CCl4诱导的肝纤维化模型大鼠的改善作用及可能机制。方法 将SD大鼠随机分为正常组、模型组、水飞蓟宾组(30 mg·kg–1)、黄芪甲苷组(14 mg·kg–1)。采用50% CCl4橄榄油溶液(1.5 mL·kg–1)腹腔注射建立肝纤维化模型,每周2次,持续8周。然后各组大鼠按照每天10 mL·kg–1灌胃相应药物,共4周。检测大鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)含量;计算肝脏指数;苏木素-伊红(HE)及Masson染色观察肝组织病理变化;Western blotting检测转化生长因子(TGF-β1)、上皮间质转化标志物E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)和α-平滑肌动蛋白(α-SMA)的蛋白表达水平;实时荧光定量PCR检测TGF-β1和E-cadherin的mRNA表达水平。结果 与正常组相比,模型组大鼠肝脏指数显著升高(P<0.01),血清中ALT、AST含量明显上升(P<0.01),胶原容积分数明显增加(P<0.01),肝组织内E-cadherin蛋白表达明显下降(P<0.01),α-SMA、N-cadherin蛋白表达明显升高(P<0.01),TGF-β1 mRNA及蛋白表达水平明显上升(P<0.05或P<0.01)。与模型组比较,黄芪甲苷组肝脏指数大幅下降(P<0.01),血清中ALT和AST含量明显降低(P<0.01),胶原容积分数明显下降(P<0.01),肝组织内E-cadherin蛋白表达上调(P<0.05),α-SMA、N-cadherin蛋白表达显著下调(P<0.01),TGF-β1蛋白和mRNA表达下降(P<0.01或P<0.05)。结论 黄芪甲苷对CCl4诱导肝纤维化模型大鼠具有改善作用,其机制可能与下调N-cadherin、α-SMA、TGF-β1蛋白表达,上调E-cadherin蛋白表达有关。 相似文献
3.
Zhang Y Csanaky IL Cheng X Lehman-McKeeman LD Klaassen CD 《Toxicological sciences》2012,127(2):451-462
Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na(+)-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance-associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis. 相似文献
4.
目的探讨骨形态发生蛋白9(BMP-9)在胆道闭锁(BA)肝纤维化中的作用机制。方法选取14例BA患儿肝组织标本为BA组,5例胆总管囊肿(CBD)患儿肝组织标本为CBD组,HE染色对肝组织进行肝纤维化评估,免疫组化染色检测BMP-9、p-SMAD1/5表达情况,实时荧光定量逆转录聚合酶链反应(qPCR)检测肝组织BMP-9及DNA结合抑制因子1(ID1)mRNA表达水平。培养人肝星状细胞LX-2,用重组转化生长因子(rTGF)-β1与重组BMP(r BMP)-9处理,蛋白质印迹法检测细胞中SMAD1/5、p-SMAD1/5、ID1蛋白及α-平滑肌肌动蛋白(α-SMA)表达情况,qPCR检测细胞中α-SMA及ID1 mRNA表达情况。结果 BA组肝组织中BMP-9及p-SMAD1/5蛋白、BMP-9及ID1mRNA表达水平均高于CBD组;在BA组中重度肝纤维化患儿BMP-9蛋白、BMP-9及ID1 m RNA的表达高于轻度肝纤维化患儿(P<0.05)。LX-2细胞经rTGF-β1、rBMP-9处理后,α-SMA蛋白及α-SMA m RNA表达水平均升高(P<0.05)。LX-2... 相似文献
5.
《International immunopharmacology》2014,21(2):352-357
Protease-activated receptor (PAR) 2 is a G-protein-coupled receptor that is activated by mast cell tryptase. PAR-2 activation augments profibrotic pathways through the induction of extracellular matrix proteins. PAR-2 is widely expressed in hepatic stellate cells (HSCs), but the role of tryptase/PAR-2 interaction in liver fibrosis is unclear. We studied the development of bile duct ligation (BDL)-induced hepatic fibrosis in rats treated with mast cell tryptase inhibitor APC 366, and showed that APC 366 reduced hepatic fibrosis scores, collagen content and serum biochemical parameters. Reduced fibrosis was associated with decreased expression of PAR-2 and α-smooth muscle actin (α-SMA). Our findings demonstrate that mast cell tryptase induces PAR-2 activation to augment HSC proliferation and promote hepatic fibrosis in rats. Treatment with tryptase antagonists may be a novel therapeutic approach to prevent fibrosis in patients with chronic liver disease. 相似文献
6.
Jae Ho Choi Yong Pil Hwang Chul Yung Choi Young Chul Chung Hye Gwang Jeong 《Food and chemical toxicology》2010
In current study, we investigated the protective effects of the anthocyanin fraction (AF) obtained from the purple-fleshed sweet potato on hepatic fibrosis induced by dimethylnitrosamine (DMN) administration in rats. Treatment with DMN for 4 weeks produced marked liver fibrosis as assessed by increased serum alanine aminotransferase and aspartate aminotransferase activity and hepatic collagen content. These increases were inhibited by treatment with AF prior to the administration of DMN. In addition, AF inhibited DMN-induced reductions in rat body and liver weights in a dose-dependent manner. Histopathological evaluation of the rat livers revealed that AF reduced the incidence of hepatic fibrosis lesions and inhibited DMN-induced increases in α-smooth muscle actin (α-SMA) and collagen type I and III expression levels. AF also decreased DMN-induced expression levels platelet-derived growth factor receptors-beta, tumor necrosis factor-alpha and transforming growth factor-beta. This study demonstrates that AF administration can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis. 相似文献
7.
Toklu HZ Dumlu MU Sehirli O Ercan F Gedik N Gökmen V Sener G 《The Journal of pharmacy and pharmacology》2007,59(9):1287-1295
Punica granatum L. (pomegranate) is a widely used plant that has high nutritional value. The aim of this study was to assess the effect of chronic administration of pomegranate peel extract (PPE) on liver fibrosis induced by bile duct ligation (BDL) in rats. PPE (50 mg kg(-1)) or saline was administered orally for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage. Proinflammatory cytokines (tumor necrosis factor-alpha and interleukin 1 beta) in the serum and antioxidant capacity (AOC) were measured in plasma samples. Samples of liver tissue were taken for measurement of hepatic malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence assay. Serum AST, ALT, LDH and cytokines were elevated in the BDL group compared with the control group; this increase was significantly decreased by PPE treatment. Plasma AOC and hepatic GSH levels were significantly depressed by BDL but were increased back to control levels in the PPE-treated BDL group. Increases in tissue MDA levels and MPO activity due to BDL were reduced back to control levels by PPE treatment. Similarly, increased hepatic collagen content in the BDL rats was reduced to the level of the control group with PPE treatment. Thus, chronic PPE administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic structure and function. It therefore seems likely that PPE, with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver from fibrosis and oxidative injury due to biliary obstruction. 相似文献
8.
Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin significantly attenuated the severity of BDL-induced hepatic injury and fibrosis by attenuating oxidative stress and inflammation. Taken together, these findings suggest that gastrodin might be an effective antifibrotic drug in cholestatic liver disease. 相似文献
9.
Liver fibrosis is a consequence of chronic liver disorders which lead to the accumulation of extracellular matrix (ECM). Particularly, there is an increased accumulation of collagen in the fibrotic liver. We have therefore used a triplex forming oligonucleotide (TFO) against the type α1(I) collagen and evaluated, whether it can attenuate liver fibrosis induced by common bile duct ligation (CBDL) in rats. There was a significant decrease in hydroxyproline levels and Masson's trichrome staining for collagen in TFO-treated CBDL groups compared to non-treated CBDL group. There was over expression of type α1(I) collagen, α-smooth muscle actin (α-SMA) and TGF-β1 expression in the CBDL group compared to TFO-treated CBDL group. Also, the serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were less in the TFO treated group compared to non-treated CBDL group. There was also less neutrophils accumulation in TFO treated CBDL group assayed by myeloperoxidase (MPO) assay. These results suggests that TFO can be used to downregulate type 1 collagen gene expression and can alleviate liver fibrosis induced by common bile duct ligation. 相似文献
10.
目的观察荔枝核总黄酮对胆汁淤积性肝纤维化大鼠肝功能指标的影响及对胶原蛋白的影响,探讨其可能的干预机制。方法将胆总管结扎后的SD大鼠分为胆总管结扎组(BDL组),荔枝核总黄酮组(TlFL组),水飞蓟宾组(SIL组),以假手术组为阴性对照。四周后处死大鼠,取血清检测各组大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、直接胆红素(BILD2)、总胆红素(BILT2)、肌酐(CREJ2)、血尿素氮(UREAL),同时,取肝组织行HE、Masson染色,westernblot测定各组肝组织的PC3、PCI、p16的表达。结果与BDL组比较,TFL组血清SOD含量明显升高(P〈0.05),ALT,AST,BILD2,BILT2水平明显降低(P〈0.05),明显改善大鼠肝纤维化程度(P〈O.05),且对肾功能无明显影响(P〉0.05),TFL可明显抑制p16、PC3、PCI蛋白的表达(P〈0.05)。结论TFL组(300mg,/kg·d)有明显改善胆汁淤积及减轻肝组织纤维化的作用且对肾功能无明显影响,明显抑制胆汁淤积性肝纤维化大鼠肝脏p16、PC3、PCI蛋白的表达,可能是通过诱导细胞凋亡途径抑制肝纤维化。 相似文献
11.
鬼针草总黄酮对免疫性肝纤维化大鼠胶原代谢的影响及机制 总被引:1,自引:0,他引:1
目的探讨鬼针草总黄酮(TFB)对免疫性肝纤维化大鼠胶原代谢的影响及机制。方法 SD大鼠随机分为正常组、模型组、TFB大、中、小剂量组和秋水仙碱阳性药对照组,采用腹腔注射猪血清诱导肝纤维化模型,造模后灌服相应的受试药物。ELISA法测定大鼠血清Ⅲ型前胶原酶(PCⅢ)、Ⅳ型胶原酶(CⅣ)含量;免疫组化法测定肝组织中Ⅰ型胶原蛋白的表达;RT-PCR技术检测肝组织中Ⅰ型胶原、α-SMA、TGF-β1 mRNA的表达情况;Western blot检测肝组织中Smad2蛋白的表达。结果与模型组相比,TFB能明显降低肝纤维化大鼠血清中PCⅢ、CⅣ含量,抑制肝组织中Ⅰ型胶原、α-SMA、TGF-β1 mRNA及Ⅰ型胶原、Smad2蛋白的表达。结论 TFB能明显降低免疫性大鼠肝纤维化胶原含量,其机制可能与降低TGF-β1表达进而抑制肝星状细胞活化减少胶原生成有关。 相似文献
12.
目的研究贝那普利对大鼠肝纤维化程度及对肝纤维化大鼠TGF~β1和α-SMA表达的影响。方法建立40%CCL诱导的大鼠肝纤维化模型,42只大鼠分为对照组(n=10)、模型组(n=16)、观察组(n=16)。对3组大鼠肝组织进行HE染色、网状纤维染色、免疫组织化学染色,观察肝组织病理变化、纤维增生及TGF—β1和α-SMA的表达情况。结果模型组的肝纤维化程度、TGF—β1阳性表达、α-SMA阳性表达计分明显高于对照组,差异有统计学意义(P〈0.01);观察组的肝纤维化程度、TGF—β1阳性表达、α-SMA阳性表达计分明显低于模型组,差异有统计学意义(P〈0.05)。结论贝那普利可有效降低肝组织TGF—β1和α—SMA的表达,从而抑制大鼠肝纤维化的进程。 相似文献
13.
目的观察姜黄素衍生物(Curc-OEG)抗肝纤维化作用及其机制。方法将雄性SD大鼠共分成4组:正常组、模型组、姜黄素衍生物组和姜黄素组。用四氯化碳诱导大鼠形成肝纤维化模型,2个治疗组分别尾静脉注射100 mg·kg-1Curc-OEG和灌胃400 mg·kg-1姜黄素。10周后,测肝功及肝纤维化指标、肝组织羟脯氨酸(Hpy)水平;HE、天狼星红染色,免疫组化法观察TGF-β1及α-SMA表达;RT-PCR法测TGF-β1 mRNA水平;Western blot测TGF-β1及α-SMA蛋白表达。结果与模型组比较,Curc-OEG能改善肝功及降低肝纤维化指标,降低Hpy含量及肝纤维化程度,抑制TGF-β1及α-SMA的表达。结论 Curc-OEG具有明显的抗肝纤维化作用。 相似文献
14.
Hepatic stellate cells (HSCs) play a key role in the pathogenesis of liver fibrosis. In chronic liver injury, HSCs undergo transdifferentiation to an activated myofibroblastic phenotype and migrate to injured areas in response to chemotactic factors, producing extracellular matrix proteins such as collagen type I to repair the damage as well as overexpression of α-smooth muscle actin (α-SMA). Paeoniae Radix, the root of Paeonia lactiflora Pall, was investigated for PDGF-BB-induced HSC chemotaxis. Rat HSCs and LX-2, a human HSC cell line, were used for the in vitro experiments. Cell migration was analyzed by wound-healing and transwell assays. An ELISA and a Sircol collagen assay kit were used to detect the expressions of α-SMA and of collagen, respectively. Phosphorylations of mitogen-activated protein kinases, including ERK 1/2, p38, and JNK, were evaluated with immunoblotting. Results indicated that PDGF-BB increased migration as well as α-SMA and collagen expression in HSCs. Paeoniae Radix extracts and its active components, paeonol and 1,2,3,4,6-penta- O-galloyl- β-D-glucose (PGG), inhibited PDGF-BB-induced HSC migration and α-SMA and collagen expressions in a concentration-dependent manner. The inhibitory effects were associated with downregulation of PDGF receptor- α, ERK, p38, and JNK activation. Both paeonol and PGG participate in HSC migration, but via differential mechanisms. 相似文献
15.
目的观察雷公藤红素(Celastrol,Cel)对二乙基亚硝胺(DEN)诱导大鼠肝纤维化的治疗作用及机制。方法采用DEN诱导大鼠肝纤维化模型,分为正常对照组、模型组、Cel给药组(2、4、8 mg.kg-1)和秋水仙碱组(Col,0.1 mg.kg-1)。紫外分光光度法检测各组大鼠血清中AST、ALT、肝组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及肝组织中丙二醛(MDA)、羟脯氨酸(HYP)的含量;ELISA检测大鼠血清中透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCIII)、Ⅳ型前胶原(CIV)、TGF-β1的含量;Western blot检测肝脏α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)和TGF-β1蛋白的表达;HE染色观察肝组织病理形态学变化;Masson染色观察肝组织中胶原沉积变化。结果与模型组比较,Cel能明显降低肝纤维化大鼠血清中升高的TGF-β1、ALT、AST、HA、LN、PCIII含量,降低肝组织中升高的HYP和MDA的含量,明显升高肝组织中SOD和GSH-Px酶活性,减少肝纤维化大鼠肝组织中α-SMA、Col I和TGF-β1的表达,改善其肝脏病理损伤程度,减少肝脏中胶原沉积。结论 Cel对肝纤维化大鼠有很好的治疗作用,其作用机制可能与Cel的抗氧化作用,降低TGF-β1的表达,抑制HSC活化,抑制胶原合成有关。 相似文献
16.
In this study, the protective effect of extract of Hsian-tsao (Mesona procumbens) (EHT) against liver fibrogenesis in carbon tetrachloride (CCl4)-injured rats was evaluated. The inhibitory effect of oleanolic acid (OA) and ursolic acid (UA), which are the active compounds in EHT, on the activation of hepatic stellate cells (HSC) was also determined. The results showed that EHT at a dosage of 1.2 g/kg of b.w. significantly reduced the liver injury induced by CCl4 in rats. It also decreased the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and the deposition of collagen in the liver. Oral administration of EHT reduced the levels of alpha-smooth muscle actin (α-SMA) and the activity of metalloproteinases (MMPs) in rats injured by treatment with CCl4. In addition, we performed experiments with the rat hepatic stellate cell line HSC-T6 in which we induced the expression of MMP-2 and α-SMA with phorbol-12-myristate-13-acetate (PMA). Treating these cells with OA (20 μM) or UA (10 μM) caused a decrease in the levels of both proteins. Taken together, our data indicate that EHT can efficiently inhibit CCl4-induced liver fibrosis in rats. EHT may therefore be a useful functional food for preventing liver fibrosis. 相似文献
17.
青蒿琥酯抗大鼠免疫性肝纤维化的作用及机制研究 总被引:7,自引:0,他引:7
目的研究青蒿琥酯抗实验性肝纤维化的作用及其可能机制。方法制备牛血清白蛋白免疫性大鼠肝纤维化模型。动物随机分为6组:正常对照组、模型对照组、Art组(5、15、45 mg.kg-1)、阳性对照Col组(0.1 mg.kg-1)。Masson染色观察肝组织病理变化,Jamall法测定肝组织中羟脯氨酸(Hyp)的含量,RT-PCR技术检测肝组织转化生长因子β1(TGF-β1),α-肌动蛋白(α-SMA)mRNA的表达。体外培养大鼠肝星状细胞株(HSC-T6),用TGF-β1(5μg.L-1)刺激,与Art(终浓度6.25、25、50 mg.L-1)共培养后,检测HSC-T6中Ⅰ型前胶原(procollagenⅠ)mRNA及Ⅰ型胶原(collagenⅠ)蛋白的表达。结果与模型组相比,Art各组能减轻肝组织纤维增生的程度,降低肝组织Hyp含量,使肝组织α-SMA、TGF-β1 mRNA和HSC-T6中procollagenⅠmRNA和collagenⅠ蛋白的表达水平下降。结论 Art有明显的抗肝纤维化作用,其机制可能与抑制HSC活化,降低TGF-β1 mR-NA及collagenⅠ蛋白的表达有关。 相似文献
18.
目的研究抑制活化素受体样激酶(ALK)5对增生性瘢痕成纤维细胞Ⅰ型胶原蛋白(COL1A2)和α-平滑肌肌动蛋白(α-SMA)表达的影响。方法手术取增生性瘢痕组织进行成纤维细胞体外原代培养,采用不同浓度(1、5、10μM)的ALK5抑制剂CP-639180对增生性瘢痕成纤维细胞干预3 h后,分别采用定量逆转录PCR和Western blot方法检测Ⅰ型胶原蛋白和α平滑肌肌动蛋白的表达。结果与对照组比较,ALK5抑制剂处理后,成纤维细胞中COL1A2的mRNA和蛋白含量均明显降低,且COL1A2的mRNA和蛋白水平与抑制剂的浓度呈反比(P<0.05,P<0.01)。同样,ALK5抑制剂在转录水平和蛋白翻译水平降低了瘢痕成纤维细胞中α-SMA的表达(P均<0.05)。结论应用小分子ALK5抑制剂CP-639180可以抑制增生性瘢痕成纤维细胞分泌Ⅰ型胶原蛋白和α-SMA,进一步抑制胶原纤维的合成,为增生性瘢痕治疗研究提供新的思路。 相似文献
19.
Effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes
Qiang G Zhang L Yang X Xuan Q Shi L Zhang H Chen B Li X Zu M Zhou D Guo J Yang H Du G 《European journal of pharmacology》2012,685(1-3):156-164
Currently there is no effective treatment for nonalcoholic fatty liver disease (NAFLD), especially hepatic fibrosis induced by type 2 diabetes. Valsartan maybe has beneficial effect on the liver disease. The aim of the present study was to investigate the effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes. An animal model of hepatic fibrosis with type 2 diabetes was developed using a high-sucrose, high-fat diet and low-dose streptozotocin. Valsartan (15 mg/kg/day, i.g.) was orally administered for four months. The livers were removed to make hematoxylin-eosin (HE) staining and Picric acid-Sirius red staining, and immunohistochemistry staining of α-smooth-muscle-actin (α-SMA), transforming growth factor β1 (TGF-β1), tumor necrosis factor (TNF-α) and monocyte chemotactic protein-1 (MCP-1). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect hepatocyte apoptosis. The liver mitochondria were isolated to measure the mitochondrial respiratory function. The results showed that valsartan significantly alleviated the lesion of hepatic steatosis and hepatic fibrosis by HE staining and Picric acid-Sirius red staining. Immunohistochemical staining suggested that the expression of α-SMA, TGF-β1, TNF-α and MCP-1 in liver tissue of diabetic rats was markedly reduced by valsartan. TUNEL staining showed that there were fewer TUNEL-positive apoptotic hepatocytes in valsartan group. In addition, valsartan restored the injured hepatic mitochondrial respiratory function. The findings demonstrated that valsartan prevented the pathological progression of hepatic fibrosis in type 2 diabetic rats, correlated with reducing α-SMA, TGF-β1, TNF-α and MCP-1 expression, also anti-apoptosis and mitochondria-protective potential. 相似文献
20.
摘要: 目的 探讨夏枯草硫酸多糖 (PVSP) 对四氯化碳 (CCl4 ) 致大鼠纤维化的干预作用。方法 采用 CCl4-橄榄油腹腔注射诱导建立 SD 大鼠肝纤维化模型, 将造模成功的大鼠随机分成 3 组, 每组 10 只, 分别为模型组 (Model 组)、 PVSP 高剂量组 (PVSP-H 组: 400 mg/kg) 和 PVSP 低剂量组 (PVSP-L 组: 100 mg/kg)。并设空白对照组 (Blank 组) 和溶剂对照组 (Solvent 组)。采用全自动生化分析仪测定血清丙氨酸转氨酶 (ALT) 和天冬氨酸转氨酶 (AST) 的含量, HE 和天狼猩红染色比较炎症及肝纤维化程度; 采用 qRT-PCR 和免疫组织化学分析肝组织中Ⅰ型胶原 (Col- Ⅰ)、 平滑肌肌动蛋白 (α-SMA) mRNA 和蛋白的表达量。结果 Solvent 组大鼠血清中 ALT、 AST 及肝组织中 Col-Ⅰ、 α-SMA mRNA 和蛋白与 Blank 组相比差异均无统计学意义; 与 Model 组相比, PVSP 能显著降低血清 ALT 和 AST (P<0.05); HE 和天狼猩红染色结果显示 PVSP 能减轻炎症及纤维化程度; qRT-PCR 和免疫组织化学结果显示 PVSP 明显降低大鼠肝脏内 Col-Ⅰ、 α-SMA mRNA 和蛋白表达 (P<0.05)。结论 PVSP 具有减轻大鼠肝纤维化作用, 其机制可能与抑制Col-Ⅰ、 α-SMA 表达, 减少细胞外基质的生成并促进细胞外基质的降解有关。 相似文献