Galectin-3在CCl4所致肝损伤的保护作用

目的探讨Galectin-3在CC l4所致急性肝损伤中的作用。方法选择ICR系的雄性Galectin-3基因敲除型(Gal-3(-/-))和其野生型(Gal(+/+))小鼠,一次灌胃给予CC l4,观察给药后10 h、24 h、48 h和72 h的肝组织病理改变和检测其血清谷草转氨酶(AST)和谷丙转氨酶(ALT)活性。结果与Gal(+/+)型鼠比较,CC l4对Gal-3(-/-)型鼠的肝组织病理损伤出现时间早、损伤重。Gal-3(-/-)型鼠在CC l4灌胃后10 h和24 h的血清ALT活性及CC l4灌胃后10 h的血清AST活性与Gal(+/+)型鼠比较有显著升高。结论Galectin-3蛋白在CC l4致急性肝损伤中具有保护作用。     

急性CCl4肝损伤的研究进展

急性四氯化碳 (CCl4 )肝损伤时肝脏中自由基清除剂和细胞因子 ,粘附分子会发生变化并在此过程中起作用 ,或促进肝损伤或预防肝损伤。许多对肝脏具有保护作用的中、西药物其作用机制各不相同。     

CCl4致小鼠急性肝损伤模型的研究

目的建立稳定的CCl4小鼠急性肝损伤动物模型。方法观察小鼠性别、给药剂量、测定方法、动物质量因素对CCl4所致急性肝损伤模型小鼠血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）水平的影响。结果动物性别对肝损伤模型动物ALT检测指标有一定的影响,0.1%浓度CCl4作为造模浓度较适宜,肝损伤模型动物ALT、AST指标机测较手测准确、简便,动物质量因素对CCl4肝损伤动物模型影响较大。结论 CCl4致小鼠急性肝损伤模型效果受动物性别、给药剂量和动物质量因素影响较大,各实验室应进行标准化研究,以保证CCl4急性肝损伤动物模型的稳定性。     

富硒酵母对CCl4肝损伤小鼠免疫功能的影响

目的:研究富硒酵母对CCl4肝损伤小鼠免疫功能的影响.方法:将50只小鼠随机分为空白组、模型组、硒酵母组、维生素E(VE)组和混合绀(混合喂食硒酵母和VE),每组10只.空白组和模型组灌胃蒸馏水,硒酵母组灌胃富硒酵母,VE组灌胃VE,混合组同时灌胃和硒酵母组、VE组等量的酵母和VE,连续30 d.实验结束后一次性给予8 g/LCCl4的香油溶液5 mL/kg,空白组给香油.然后测定小鼠T和B淋巴细胞转化率、NK细胞活性和巨噬细胞的吞噬功能.结果:富硒酵母能够显著提高小鼠T和B淋巴细胞转化率、NK细胞活性和巨噬细胞的吞噬功能,且和VE具有协同作用.结论:富硒酵母能提高CCl4肝损伤小鼠的免疫功能.     

丹参酮IIA对CCl4诱导小鼠急性肝损伤的保护作用

目的 研究丹参酮IIA(tanshinone ⅡA, Tan ⅡA)对CCl4诱导小鼠急性肝损伤的抗氧化、保护作用及其可能的作用机制。 方法 将C57BL/6J小鼠随机分成正常组、CCl4组以及Tan ⅡA保护组(Tan ⅡA 20 mg/kg+CCl4),每组10只。腹腔注射CCl4构建小鼠急性肝损伤模型。计算各组小鼠的肝脏指数,检测血清AST和ALT活性,测定肝组织SOD活性及GSH、MDA含量,HE染色观察肝组织病理变化,免疫组织化学法和Western blot检测肝组织PI3K、p-PI3K、Akt、p-Akt、Nrf2和HO-1蛋白表达水平。 结果 与CCl4组相比,Tan ⅡA保护组肝脏指数显著下降(P<0.01),血清AST(P<0.01)和ALT活性降低(P<0.05),肝组织SOD活性(P<0.01)及GSH含量升高(P<0.05),MDA含量降低(P<0.05),肝组织病理变化得到显著改善。同时,Tan ⅡA使肝组织p-PI3K和p-Akt表达水平明显升高(P<0.01),显著诱导Nrf2转位入核(P<0.01),促使其下游靶蛋白HO-1表达水平明显升高(P<0.01)。 结论 Tan ⅡA能够显著改善CCl4诱导的急性肝损伤,其机制可能与PI3K/Akt/Nrf2/HO-1信号通路有关。     

牡蛎粉对化学性肝损伤保护作用的实验研究

目的探讨牡蛎粉对化学性肝损伤的保护作用.方法对NIH种小鼠每日经口灌胃给予0.15g/kg、0.75g/kg和3.00g/kg的牡蛎粉.4周后,以0.1ml/10g的剂量一次性经腹腔注射给予0.1%CCl4.结果 3.00g/kg剂量组的血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST))水平降低,与CCl4对照组比较(p<0.01);0.75g/kg和3.00g/kg剂量组发生肝细胞气球样变的动物例数明显减少,病变程度减轻,气球样变评分低于CCl4对照组(p<0.01).结论牡蛎粉对CCl4化学性肝损伤具有保护作用.     

敲除Colgalt2基因加重小鼠急性肝损伤

目的：初步探讨Colgalt2基因介导的胶原Glcα1,2 Galβ1?糖基化修饰在急性肝损伤过程中的作用。方法取60只Colgalt2＋／＋小鼠和60只Colgalt2－／－小鼠进行急性肝损伤实验,雌雄各半。每组随机选取20只小鼠腹腔注射CCl4（CCl4∶橄榄油＝2∶7,20 ml／kg）。观察小鼠死亡情况,并绘制生存曲线。每组剩余40只小鼠随机分为0、4、8、12 h组,每组10只,腹腔注射CCl4（剂量同上）。分别于0、4及8 h各处死6只小鼠,之后将4及8 h组剩余的小鼠均纳入12 h组（ Colgalt2＋／＋小鼠, n＝14; Colgalt2－／－小鼠, n＝16）,并于12 h处死小鼠。 HE染色观察肝组织的病理学改变,取血清进行生化指标ALT、 AST测定。利用qRT?PCR和Western印迹技术检测小鼠Colgalt2在基因及蛋白水平的表达情况。结果Colgalt2基因在Col?galt2＋／＋小鼠肝组织内表达,而在Colgalt2－／－小鼠肝组织内不表达。注射CCl4后10 h, Colgalt2＋／＋小鼠死亡率为35％, Colgalt2－／－小鼠死亡率为70％,两组小鼠死亡率差异显著（P＜0．05）。注射CCl4后12 h, Colgalt2＋／＋小鼠死亡率达50％, Colgalt2－／－小鼠死亡率为70％,差异不显著（P＞0．05）。肝功检测及HE染色结果均提示,与Colgalt2＋／＋小鼠相比, Colgalt2－／－小鼠肝损伤较重。注射CCl4后,野生型小鼠Colgalt2在RNA水平和蛋白水平表达下调。结论 Colgalt2基因敲除在一定程度上可加重小鼠急性肝损伤。该观察结果提示, Colgalt2基因介导的胶原Glcα1,2 Galβ1?糖基化修饰可能与肝损伤的修复有关。     

解毒护肝合剂对CCl4致大鼠肝损伤的影响

本文研究了解毒护肝合剂对CCl_4致大鼠肝损伤的保护作用,在CCl_4致大鼠肝损伤模型上,解毒护肝合剂可明显降低CCl_4致大鼠SGPT升高,同时能使CCl_4致肝脏病理组织学损伤明显减轻,表明解毒护肝合剂对CCl_4致大鼠肝损伤有一定保护作用,其作用可能与减轻肝细胞变性、坏死有关。     

金丝桃苷对溃疡性结肠炎大鼠的保护作用及机制研究

目的 观察金丝桃苷(Hyp)对三硝基苯磺酸(TNBS)诱导的大鼠溃疡性结肠炎(UC)的治疗作用,并初步探讨其作用机制.方法 直肠给予Wistar大鼠TNBS/乙醇溶液以复制大鼠UC模型,灌胃给予低、中、高剂量的Hyp(25、50、100 mg/kg)对其进行治疗,于给药7d后处死大鼠,观察结肠大体、组织病理学及湿质量指...     

Quercetin protects against lipopolysaccharide-induced acute lung injury in rats through suppression of inflammation and oxidative stress

Introduction

Acute lung injury (ALI) is an acute inflammatory disease characterized by excess production of inflammatory factors in lung tissue. Quercetin, a herbal flavonoid, exhibits anti-inflammatory and anti-oxidative properties. This study was performed to assess the effects of quercetin on lipopolysaccharide (LPS)-induced ALI.

Material and methods

Sprague-Dawley rats were randomly divided into 3 groups: the control group (saline alone), the LPS group challenged with LPS (Escherichia coli 026:B6; 100 µg/kg), and the quercetin group pretreated with quercetin (50 mg/kg, by gavage) 1 h before LPS challenge. Bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected 6 h after LPS administration. Histopathological and biochemical parameters were measured.

Results

The LPS treatment led to increased alveolar wall thickening and cellular infiltration in the lung, which was markedly prevented by quercetin pretreatment. Moreover, quercetin significantly (p < 0.05) attenuated the increase in the BALF protein level and neutrophil count and lung wet/dry weight ratio and myeloperoxidase activity in LPS-challenged rats. The LPS exposure evoked a 4- to 5-fold rise in BALF levels of tumor necrosis factor-α and interleukin-6, which was significantly (p < 0.05) counteracted by quercetin pretreatment. Additionally, quercetin significantly (p < 0.05) suppressed the malondialdehyde level and increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in the lung of LPS-treated rats.

Conclusions

Quercetin pretreatment effectively ameliorates LPS-induced ALI, largely through suppression of inflammation and oxidative stress, and may thus have therapeutic potential in the prevention of this disease.     

Hepatoprotective effects of phloretin against CCl4-induced liver injury in mice

This study was designed to characterize the protective capacity of phloretin against acute liver oxidative injury induced by CCl₄ in mice. Administration of phloretin at 100, 200 and 500?mg/kg·bw orally daily in mice for 21 consecutive days, prior to intraperitoneal injection of 0.5% CCl₄/peanut oil (ip, 0.3?mL), significantly reduced the CCl4-induced inhibition of serum alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase activities. Furthermore, phloretin elevated glutathione and superoxide dismutase activities and reduced formation of malonaldehyde in the liver of mice, when compared with CCl₄-intoxication mice. Moreover, phloretin also prevented the CCl₄-caused liver histological alteration, as indicated by histopathological evaluation. These data collectively demonstrated the potential prospect of phloretin as functional ingredient to prevent liver injury.     

Protective effects of pentoxifylline on acute liver injury induced by thioacetamide in rats

Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with the effects of antioxidation, anti-inflammation and anti-fibrosis that has been shown to induce damage in liver. The purpose of this study is to investigate the effects and possible mechanisms of PTX on thioacetamide (TAA)-induced acute liver injury in rats. Male Sprague-Dawley (SD) rats were divided into four groups: control, PTX, TAA and PTX+TAA treated groups. Rats were administrated TAA together with or without PTX for a week and sacrificed 24 h after the last intragastric administration of PTX. Histopathological analysis was carried out. The liver function, the indices of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in liver tissues, and pro-inflammatory cytokines expressions were examined. The mRNA level of NF-κB p65 in liver was also determined. PTX significantly attenuated TAA-induced liver injury. The serum transaminase and MDA levels were reduced while the levels of SOD and GSH were increased, as compared with the TAA-treated group. PTX also remarkably suppressed the secretions of pro-inflammatory cytokines and the nuclear factor-κB (NF-κB) activation induced by TAA. In addition, the histopathological analysis showed that the range and degree of liver tissue lesions were improved obviously in PTX treated group. Pentoxifylline could ameliorate the effects of thioacetamide-induced acute liver injury in rats by inhibiting oxidative stress, expressions of pro-inflammatory cytokines and NF-κB activation.     

Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized [1‐13C]pyruvate

To facilitate diagnosis and staging of liver disease, sensitive and non‐invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized ¹³C‐pyruvate to assess metabolic parameters in a CCl₄ model of liver damage in rats. Dynamic 3D ¹³C chemical shift imaging data from a volume covering kidney and liver were acquired from 8 control and 10 CCl₄‐treated rats. At 12 time points at 5 s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine, and lactate. These measurements were compared with standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl₄‐treated but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with these results, metabolic imaging revealed an increased alanine/pyruvate ratio in liver of CCl₄‐treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl₄‐treated compared with control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using ¹³C‐pyruvate can be a successful tool to non‐invasively assess liver damage in vivo. Copyright © 2015 John Wiley & Sons, Ltd.     

Protective effect of blueberry anthocyanins in a CCl4-induced injury model in human embryonic liver cells

This study investigates the possible mechanism of the protective effects of blueberry anthocyanins on human embryonic liver L-02 cells. Results of the WST-8 method showed that different concentrations of blueberry anthocyanins protected the human embryonic liver L-02 cells against CCl₄-induced injury in a dose-dependent manner with IC₅₀ at 6.2×g/L. Cell clone formation inhibition assay demonstrated that cell clones increased with increased concentration of anthocyanins. Propidium iodide (PI) staining analysis showed that anthocyanins can decrease cell cycle in the G1 phase. DNA ploidy analysis showed a weakened percentage of hypodiploid cells in a dose-dependent manner. Moreover, Annexin V-FITC/PI staining analysis showed a dose-dependent effect of anthocyanins on late apoptotic and necrotic cells. Western blot assay showed gradually decreased caspase-3 protein expression levels with increased anthocyanin concentration. In summary, these findings provided pharmacological evidence supporting the clinical application and protective effect of blueberry anthocyanins against acute liver injury.     

Overexpression of peptidyl-prolyl isomerase Pin1 attenuates hepatocytes apoptosis and secondary necrosis following carbon tetrachloride-induced acute liver injury in mice

Pin1, a member of the parvulin family of PPIase enzymes, plays a crucial role in the post phosphorylation regulation that governs important roles in the cell signaling mechanism and regulates a variety of cellular events. In this study, we investigated the role of Pin1 in carbon tetrachloride (CCl(4))-induced apoptosis and necrosis of hepatocytes during acute liver injury of mice. An in vivo study was done with the overexpression of Pin1 in the mouse liver; using Pin1-adenoviruse (ad-Pin1) followed by CCl(4) injection to induce acute liver injury. Pin1 overexpression in the liver of the experimental mice attenuated acute liver injury induced by CCl(4) . Serum aminotransferases and the number of apoptotic cells were decreased compared to those of control virus injected mice. In addition, Pin1 overexpression increased NF-kB activity, as evidenced by increased DNA binding. In conclusion, Pin1 reduces acute liver injury of mice due to CCl(4) by modulating apoptotic signals and by increasing NF-kB activity.     

Bark extract of Bathysa cuspidata attenuates extra-pulmonary acute lung injury induced by paraquat and reduces mortality in rats

This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ-induced extra-pulmonary ALI and mortality in rats and suggest that these effects may be associated with the inhibition of oxidative damage.     

Sesamin ameliorates oxidative liver injury induced by carbon tetrachloride in rat

Sesamin is naturally occurring lignan from sesame oil with putative antioxidant property. The present study was designed to investigate the protective role of sesamin against carbon tetrachloride induced oxidative liver injury. Male Wistar albino rats (180-200 g) were divided in to 5 groups (n=6). Hepatotoxicity was induced by the administration of CCl₄ (0.1 ml/100 g bw., 50% v/v with olive oil) intraperitoneally. Sesamin was administered in two different dose (5 and 10 ml/kg bw) to evaluate the hepatoprotective activity. Sesamin significantly reduced the elevated serum liver marker enzymes (P<0.0001). Reduction of TBARS (P<0.01 and P<0.001) followed by enhancement of GSH., SOD and catalase (P<0.0001) in liver homogenate in sesamin treated groups shows the amelioration of oxidative stress induced by CCl₄. Histopathological report also supported the hepatoprotection offered by sesamin. Sesamin effects in both the dose were in comparable to reference standard drug silymarin. From these above findings it has been concluded that sesamin ameliorate the oxidative liver injury in terms of reduction of lipid peroxidation and enhancement of liver antioxidant enzymes.     

微小RNA-7敲减对ConA诱导的小鼠急性肝损伤的影响

目的:研究微小RNA-7(miR-7)敲减(KD)对急性肝损伤(ALI)模型小鼠的影响。方法:野生型(WT)小鼠和miR-7KD小鼠腹腔注射30 mg/kg刀豆蛋白(ConA)建立急性肝损伤模型;48 h后,观察小鼠肝脏的形态、重量及其脏器指数变化;HE染色观察小鼠肝脏组织病理学变化;血清学方法检查血清中谷丙转氨酶(ALT)的水平;ELISA法检测血清中细胞因子IL-4和IFN-γ的水平;流式细胞术检测肝脏组织中CD4~+T细胞的比例及其相关的细胞因子IL-4和IFN-γ的表达变化。结果:与对照组相比,miR-7敲减后急性肝损伤小鼠的肝脏组织颜色变浅,重量减轻,重量指数明显增加(P0.05);HE染色显示miR-7KD小鼠血清炎症细胞浸润显著增多;血清学方法检测发现急性肝损伤小鼠血清ALT的水平明显上升(P0.05);ELISA法检测显示miR-7KD小鼠血清中IFN-γ水平明显升高(P0.01),而IL-4的表达水平则明显降低(P0.01);流式细胞术检测结果显示,miR-7KD小鼠肝脏中CD4+T细胞比例显著升高(P0.01),其相关的细胞因子IFN-γ的表达水平也显著上调(P0.01),而IL-4的水平没有发生明显变化。结论:敲减miR-7基因可明显促进ConA诱导的小鼠急性肝损伤。     

Exendin-4 attenuates renal tubular injury by decreasing oxidative stress and inflammation in streptozotocin-induced diabetic mice

Abstract

In this study, we aimed to research the restorative effects of exendin-4, a GLP-1 analog, on renal tubular injury in streptozotocin-induced diabetes model. BALB/c male mice were divided into four groups: non-diabetic, non-diabetic?+?exendin-4 (3?μg/kg), diabetic and diabetic?+?exendin-4. In our diabetic model, we observed renal injury mainly in tubular area rather than glomeruli and exendin-4 decreased tubular injury with its glucose lowering effect. Besides, PCNA positive tubular cells, activities of LDH and Na⁺-K⁺-ATPase were also significantly declined by the administration of exendin-4. Furthermore, exendin-4 attenuated the levels of ROS, MDA, 8-OHdG, proinflammatory cytokines (TNF-α, IL-1β), chemokine MCP-1, ICAM-1, and fibrosis-related molecules (transforming growth factor β1 and fibronectin). In consistent with reducing tubular injury, macrophage infiltration and both MCP-1 and ICAM-1 production in tubular cells were decreased. These results indicate that exendin-4 may decrease renal tubular injury seen in the beginning of diabetic nephropathy by decreasing ROS production and inflammation.