探究地龙对博来霉素诱导的肺纤维化小鼠纤维化因子TGF-β1及α-SMA表达的影响。通过Biacore技术初步检测地龙与纤维化因子TGF-β1的结合力,并采用体内药效学加以验证。将60只雌雄各半的C57小鼠随机分为空白组,模型组,地龙高、中、低剂量...探究地龙对博来霉素诱导的肺纤维化小鼠纤维化因子TGF-β1及α-SMA表达的影响。通过Biacore技术初步检测地龙与纤维化因子TGF-β1的结合力,并采用体内药效学加以验证。将60只雌雄各半的C57小鼠随机分为空白组,模型组,地龙高、中、低剂量组,醋酸泼尼松组;除空白组外(予以气管内注射0.08 m L·kg^-1氯化钠注射液),其余5组予以气管内注射博来霉素4 mg·kg^-1来复制肺纤维化模型。药物治疗14 d后,采用Masson染色、免疫组化、RT-PCR技术检测TGF-β1及α-SMA的表达。Biacore实验结果显示,地龙提取液在体外与TGF-β1蛋白有较好的结合,结合值达到619.3;Masson结果显示,与模型组相比,地龙高、中、低剂量组纤维素沉积均有不同程度减轻;RT-PCR结果显示,不同剂量的地龙提取液在一定程度上均能降低TGF-β1和α-SMA蛋白及mRNA的表达,且呈现一定的剂量依赖性。综上所述,地龙可通过与靶蛋白TGF-β1结合从而抑制α-SMA的表达来延缓肺纤维化进程。展开更多
Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lea...Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix(ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma(HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor(TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells(HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase(MAPK), toll-like receptor(TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease(NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor(VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases.展开更多
AIM: Hepatic fibrogenesis has close relation with hepatic stellate cells (HSC)and tissue inhibitors of metalloproteinase (TIMP). Oxymatrine (OM) is a kind of Chinese herb that is found to have some effects on liver fi...AIM: Hepatic fibrogenesis has close relation with hepatic stellate cells (HSC)and tissue inhibitors of metalloproteinase (TIMP). Oxymatrine (OM) is a kind of Chinese herb that is found to have some effects on liver fibrosis. We aimed to determine the effects of OM on hepatic fibrosis and explore the possible mechanism. METHODS: Thirty-two rats were randomly divided into four groups; 16 were used to develop hepatic fibrosis by carbon tetrachloride (CCI4) and treated with or without OM, and 16 were used as controls. The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and α-smooth muscle actin (α-SMA) in the livers of rats was detected by immunohisto-chemical assay. Liver pathology was determined by H&E staining and reticulum staining. RESULTS: In CCl4-injured rats, the normal structure of lobules was destroyed, and pseudolobules were formed. Hyperplasia of fibers was observed surrounding the lobules. While the degree of fibrogenesis in liver tissues was significantly decreased in those rats with OM-treatment compared with those without OM treatment. The pseudolobules were surrounded by strong, multi-layer reticular fibers, which netted into pseudolobules in CCl4-injured rats, however, there was a significant decrease in reticular fibers in OM-treated rats. The expression of TIMP-1 in hepatic cells was weak in control groups, but strong in CCl4-injured groups, however, the expression of TIMP-1 was significantly inhibited by OM (F = 52.93, P<0.05). There was no significant change in the expression of α-SMA between CCl4-injured rats with or without OM treatment (F= 8.99, P>0.05). CONCLUSION: OM effectively inhibits CCl4-induced fibrogenesis in rat liver tissues, probably by reducing the expression level of TIMP-1.展开更多
文摘探究地龙对博来霉素诱导的肺纤维化小鼠纤维化因子TGF-β1及α-SMA表达的影响。通过Biacore技术初步检测地龙与纤维化因子TGF-β1的结合力,并采用体内药效学加以验证。将60只雌雄各半的C57小鼠随机分为空白组,模型组,地龙高、中、低剂量组,醋酸泼尼松组;除空白组外(予以气管内注射0.08 m L·kg^-1氯化钠注射液),其余5组予以气管内注射博来霉素4 mg·kg^-1来复制肺纤维化模型。药物治疗14 d后,采用Masson染色、免疫组化、RT-PCR技术检测TGF-β1及α-SMA的表达。Biacore实验结果显示,地龙提取液在体外与TGF-β1蛋白有较好的结合,结合值达到619.3;Masson结果显示,与模型组相比,地龙高、中、低剂量组纤维素沉积均有不同程度减轻;RT-PCR结果显示,不同剂量的地龙提取液在一定程度上均能降低TGF-β1和α-SMA蛋白及mRNA的表达,且呈现一定的剂量依赖性。综上所述,地龙可通过与靶蛋白TGF-β1结合从而抑制α-SMA的表达来延缓肺纤维化进程。
基金Supported by National Council of Science and Technology(Conacyt)of Mexico,No.253037
文摘Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix(ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma(HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor(TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells(HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase(MAPK), toll-like receptor(TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease(NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor(VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases.
基金Supported by Foundation of "Bai Ren Ji Hua" of Shanghai Health Bureau, No. 98BR32
文摘AIM: Hepatic fibrogenesis has close relation with hepatic stellate cells (HSC)and tissue inhibitors of metalloproteinase (TIMP). Oxymatrine (OM) is a kind of Chinese herb that is found to have some effects on liver fibrosis. We aimed to determine the effects of OM on hepatic fibrosis and explore the possible mechanism. METHODS: Thirty-two rats were randomly divided into four groups; 16 were used to develop hepatic fibrosis by carbon tetrachloride (CCI4) and treated with or without OM, and 16 were used as controls. The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and α-smooth muscle actin (α-SMA) in the livers of rats was detected by immunohisto-chemical assay. Liver pathology was determined by H&E staining and reticulum staining. RESULTS: In CCl4-injured rats, the normal structure of lobules was destroyed, and pseudolobules were formed. Hyperplasia of fibers was observed surrounding the lobules. While the degree of fibrogenesis in liver tissues was significantly decreased in those rats with OM-treatment compared with those without OM treatment. The pseudolobules were surrounded by strong, multi-layer reticular fibers, which netted into pseudolobules in CCl4-injured rats, however, there was a significant decrease in reticular fibers in OM-treated rats. The expression of TIMP-1 in hepatic cells was weak in control groups, but strong in CCl4-injured groups, however, the expression of TIMP-1 was significantly inhibited by OM (F = 52.93, P<0.05). There was no significant change in the expression of α-SMA between CCl4-injured rats with or without OM treatment (F= 8.99, P>0.05). CONCLUSION: OM effectively inhibits CCl4-induced fibrogenesis in rat liver tissues, probably by reducing the expression level of TIMP-1.
