银杏叶提取物抗四氯化碳诱导的大鼠肝纤维化的实验研究

目的:探讨银杏叶提取物(GBE)抑制NF-kappa Bp65的表达在四氧化碳(CCl4)诱导Wistar大鼠肝纤维化中肝细胞损伤的意义。方法:采用CCL4诱导的大鼠肝纤维化模型。生化检测各组血清丙氨酸氨基转移酶(ALT)、天氨酸氨基转移酶(AST)。采用免疫组化S-P方法检测肝细胞NF-kappa Bp65和ICAM-1表达并分析与肝细胞损害的关系。结果:治疗组大鼠的血清肝功能指标和肝纤维化病理分级与模型组比较都有显著的改善(P<0.05);治疗组大鼠肝组织细胞因子水平与模型组比较也显著降低(P<0.05)结论:银杏叶提取物可减轻肝组织的损伤及其纤维化程度,通过抑制NF-kappa Bp65的表达,进一步减弱了ICAM-1的表达,可能是其抗肝纤维化作用的靶点之一。     

Silymarin Decreases Connective Tissue Growth Factor to Improve Liver Fibrosis in Rats Treated with Carbon Tetrachloride

Silymarin is an herbal product showing potential as protection against hepatic disorders. In an attempt to develop the agent for the treatment of hepatic fibrosis, we screened the effects of silymarin on a rat model of hepatic fibrosis induced by carbon tetrachloride (CCl₄). Intraperitoneal administration of CCl₄ to rats for 8 weeks not only increased the plasma levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) but also induced a marked increase in the formation of hepatic fibrosis. Moreover, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were also reduced in the liver of rats treated with CCl₄. Oral administration of silymarin (200 mg/kg, three times daily), in parallel, decreased the plasma levels of GOT and GPT. Furthermore, in addition to the improvement of hepatic fibrosis, the hepatic levels of hydroxyproline and connective tissue growth factor (CTGF) were both markedly decreased by silymarin. Silymarin also elevated the activities of SOD and GPx in liver isolated from CCl₄‐treated rats. The results suggest that oral administration of silymarin protects against CCl₄‐induced hepatic fibrosis in rats, likely due to the decrease in fibrotic parameters such as CTGF. Copyright © 2012 John Wiley & Sons, Ltd.     

The effect of Ginkgo biloba extract (EGb 761) on hepatic sinusoidal endothelial cells and hepatic microcirculation in CCl4 rats

It has been shown that Ginkgo biloba Extract (EGb 761) increases peripheral and cerebral blood flow and microcirculation and improves myocardial ischemia reperfusion injury. This study was designed to investigate the effect of EGb 761 on hepatic endothelial cells and hepatic microcirculation. Sixty male Wister rats were divided into normal, carbon tetrachloride (CCl4) and EGb groups, and were given normal saline, CCl4 and CCl4 plus EGb 761, respectively, for 10 weeks. Samples were taken from the medial lobe of the rat livers ten weeks later. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were observed under transmission electron microscopy (TEM). The amount of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF) and nitric oxide (NO) in liver tissue was determined by spectrophotometry and radioimmunoassay, respectively. Compared with the CCl4 group, aggregation of blood cell or micro thrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and space of Disse, injury of endothelial cells and capillization of hepatic sinusoid was significantly reduced in the EGb group. The amount of MDA, ET-1 and PAF was markedly reduced in the EGb group than in the CCl4 group, while no significant difference in the amount of NO was observed between the two groups. The results demonstrate that EGb 761 has protective effect on hepatic endothelial cells and hepatic microcirculation in rats with chronic liver injury induced by CCl4. The mechanisms may involve its inhibition on ET-1, PAF and lipid peroxidation.     

Preventive and curative effect of Lygodium flexuosum (L.) Sw. on carbon tetrachloride induced hepatic fibrosis in rats

The preventive and curative effect of Lygodium flexuosum on experimentally induced hepatic fibrosis by carbon tetrachloride (CCl(4)) was evaluated in rats. Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150 microL/100g rat weight, oral) twice a week for 10 weeks. In preventive treatment daily doses of Lygodium flexuosum n-hexane extract (200 mg/kg, p.o) was administered for 10 weeks. In curative treatment Lygodium flexuosum extract (200 mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10 weeks. Treatment with CCl(4) caused a significant decrease in body and liver weight. Lygodium flexuosum n-hexane extract prevented or reversed the decline in body and liver weight. Treatment with the extract prevented or restored the elevation of serum AST, ALT and LDH levels. Lygodium flexuosum treatment remarkably prevented or reversed an increase in liver hydroxyproline content in chronically treated rats. Histopathological changes of hepatic lesions induced by CCl(4) were significantly (p < or = 0.05) improved by treatment with Lygodium flexuosum. These results support that Lygodium flexuosum exerts effective protection in carbon tetrachloride induced hepatic fibrosis in rats.     

Hot water extracted Lycium barbarum and Rehmannia glutinosa inhibit liver inflammation and fibrosis in rats

Polysaccharide-rich Lycium barbarum and Rehmannia glutinosa have been considered to have immune-modulating activity. This study investigated the effects of water extracted Lycium barbarum and Rehmannia glutinosa (HE) on carbon tetrachloride (CCl(4))-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into: normal diet + peritoneal injection of olive oil (control), normal diet + CCl(4) injection (CCl(4)), 1 × HE (0.05% HE for each) + CCl(4) (1 × HE), and 3 × HE (0.15% HE for each) + CCl(4) (3 × HE) groups. Rats were injected with 40% CCl(4) at a dose of 0.75 ml/kg body weight once a week for seven weeks, one week after herbal extract treatment. After eight week herbal extract treatment, pathohistological examination showed that both 1× and 3 × HE treatments diminished necrotic hepatocytes, chemoattraction of inflammatory cells, and liver fibrosis. Both 1× and 3 × HE treatments decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and reduced hepatic levels of pro-inflammatory cytokines - tumor necrosis factor-α and interleukin-1β - compared to CCl(4) treatment alone. The 1 × HE treatment increased hepatic anti-inflammatory cytokine IL-10 levels. Both the 1× and 3 × HE treatments suppressed liver fibrosis biomarkers - transforming growth factor-β1 and hydroxyproline. Therefore, treatment with water extracted Lycium barbarum and Rehmannia glutinosa (0.05% and 0.15% for each) for eight weeks protects against necrotic damage, indicated by decreases in plasma ALT and AST activities, and suppresses liver fibrosis by down-regulation of liver inflammation in rats with CCl(4)-induced liver injury.     

银杏叶提取物对肝纤维化大鼠肝脏TGF-β1及其受体表达的影响

目的:观察银杏叶提取物(GbE)对肝组织TGF-β1及其受体表达的影响。方法:采用CCl4诱导大鼠肝纤维化,同时分别以200、100、50mg/kg.d的GbE进行干预,6周后取肝组织,采用免疫组化法测定肝组织TGF-β1及其受体TβRⅠ、Ⅱ、Ⅲ蛋白的表达。结果:模型大鼠肝组织TGF-β1及其受体TβRⅠ、Ⅱ、Ⅲ蛋白表达较正常组明显增高,GbE各剂量组肝组织TGF-β1及其受体表达也较模型组显著下降。结论:GbE可能通过降低TGF-β1及其受体的表达,抑制CCl4诱导的大鼠肝纤维化的发生及发展。     

Therapeutic effects and molecular mechanisms of Ginkgo biloba extract on liver fibrosis in rats

Oxidative stress can be implicated as a cause of liver fibrosis. In this sense, Ginkgo Biloba Extract (EGB), an antioxidant, may be beneficial in restraining liver fibrosis. The aim of this study was to evaluate the effects of EGB on experimental liver fibrosis. Rat liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) twice a week for 8 weeks. Three groups of rats received EGB (0.25, 0.5 and 1.0 g/kg, respectively) by stomach everyday. CCl4 administration induced liver fibrosis, which was inhibited by EGB in a dose-dependent manner. The histopathologic score of fibrosis, liver function and the levels of plasma hyaluronic acid (HA) and laminin (LN) were significantly improved in rats treated with CCl4 + EGB, compared with those treated with CCl4 only (p < 0.01 or p < 0.05). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were notably elevated, while malondialdehyde (MDA) content was significantly decreased in the rats treated with CCl4 + EGB (p < 0.01 or p < 0.05). Inhibition of hepatic stellate cell (HSC) activation and nuclear factor kappaBP65 (NF-kappaBP65) expression was demonstrated in the livers of EGB-treated rats. The activation of NF-kappaB was significantly suppressed in EGB-treated rats determined by electrophoretic mobility shift assay (EMSA). Furthermore, EGB reduced expressions of transforming growth factor-beta1 (TGF-beta1) and collagen I mRNA. In conclusion, EGB is able to ameliorate liver injury and prevent rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on HSC activation and the expression of TGF-beta1.     

JinSanE decoction, a chinese herbal medicine, inhibits expression of TGF-beta1/Smads in experimental hepatic fibrosis in rats

The study is to investigate the effects of a Chinese herbal medicine, JinSanE decoction, on the TGF-beta1/Smads signal transduction pathway in a carbon tetrachloride (CCl(4))-induced hepatic fibrosis model in rats. Rats were randomly divided into 4 study groups: namely, a normal control group, a hepatic fibrosis model group, and 2 treatment groups with different doses of JinSanE (6 and 12 g/kg). Ten rats in each group were sacrificed at 4 and 8 weeks after exposure to CCl(4) respectively. The levels of TGF-beta1 and TRII mRNA in liver tissue were analyzed by RT-PCR. The expressions of TGF-beta1, Smad3 and Smad7 in liver tissues were evaluated by immunohistochemistry. The liver histopathology was examined by hematoxylin and eosin (HE) staining and electron microscopy respectively. The liver hydroxyproline (HYP), liver function and hyaluronic acid (HA) were examined by biochemistry and radioimmunoassay (RIA) respectively. Compared with the hepatic fibrosis model group, the levels of TGF-beta1, TRII mRNA and Smad3 expression significantly decreased in the 2 treatment groups. The expression of Smad7 was significantly increased in the liver of the rats treated with JinSanE (p < 0.05 or p < 0.01). The histological changes of fibrotic liver were obviously improved in the treatment rats. The levels of liver HYP, serum liver function and HA were also remarkably improved in the treatment rats. Moreover, the effects of JinSanE occurred in a dose- and time-dependent manner in the process of the protection of liver injury and fibrosis. JinSanE decoction had a protective effect on liver injury and could ameliorate hepatic fibrosis in rats. The mechanisms might be associated with their effects of down-regulating TGF-beta1, TRII mRNA and Smad3, and up-regulating Smad7.     

抗纤Ⅰ号复方药物血清对肝星状细胞内钙离子浓度的影响

目的:研究抗纤Ⅰ号方药防治肝纤维化的分子机制,并探讨该药预防、治疗门脉高压的可行性.方法:制备大鼠含抗纤Ⅰ号药物血清,分别用药物血清和四氯化碳(CCl4)处理大鼠肝星状细胞(HSCs),作用24h后,以Fluo-3AM为细胞内Ca2 荧光指示剂负载细胞,通过激光共聚焦显微镜观察细胞内Ca2 的变化.采用正交设计方法,研究不同浓度CCl4、抗纤Ⅰ号方药物血清及其作用的先后顺序和二者作用的时间间隔对肝星状细胞内Ca2 浓度的影响.结果:不同浓度抗纤Ⅰ号方药物血清、CCl4及其作用的前后顺序对细胞内Ca2 浓度有显著影响,两因素作用的时间间隔对结果影响无显著性.CCl4在5mmol/L～15mmol/L范围内显著增加HSC内Ca2 浓度,5%～20%抗纤Ⅰ号方药物血清明显降低Ca2 浓度.结论:抗纤Ⅰ号方药物具有防治肝纤维化和门脉高压作用,其机理可能与其缓解细胞内钙超载有关.     

Traditional Chinese medicine prevents inflammation in CCl4-related liver injury in mice

Alternative medicines are being increasingly used and investigated in the management of a variety of disorders. Hepatitis is a common indication for the use of alternative therapies but evidence for the efficacy of many compounds is lacking. We have utilized a well-defined model of liver injury to study the efficacy of three herbal products designed to assist in the management of liver disease. Mice were exposed to carbon tetrachloride (CCL4) given intragastrically after they had been pretreated for five days with either saline or one of four doses of silymarin extract or CH100 (a Chinese herbal medicine comprising of 19 herbs) or one of two doses of CH101 (a Chinese herbal preparation designed to reduce fibrosis). Animals were sacrificed 24 hours after receiving CCL4. Liver enzymes and hepatic histology formed the basis for evaluating efficacy of the treatments. Each of the alternative medicines reduced the alanine amino transferase (ALT) elevation demonstrated after CCL4 injection. The high dose CH100 regimen was most effective in protecting against injury and this was confirmed with hepatic histology. Other doses of CH100, CH101 and silymarin were not shown to provide protection against the histological damage. In conclusion, Silymarin, CH100 and CH101 are able to reduce ALT elevation in animals exposed to CCL4. High dose CH100 provides protection from hepatocyte necrosis in this model. The data add to our understanding of the capacity some herbal medicines have to modify the reaction of the liver to a variety of insults and suggest the value of studying these agents further in human liver diseases.     

湖北海棠叶总黄酮抗CCl4所致大鼠肝纤维化作用研究

目的:研究湖北海棠叶总黄酮对四氯化碳(CCl4)所诱导的大鼠肝纤维化的影响,并探讨其可能的作用机制。方法:腹腔注射2ml/kg CCl4橄榄油溶液制备大鼠肝纤维化模型。首次注射后分别灌胃给药湖北海棠叶总黄酮120mg/kg和60mg/kg,每天一次,共8周。测定血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、透明质酸、羟脯氨酸、β1-转化生长因子以及肝组织中总抗氧化能力、丙二醛含量和总超氧化物歧化酶的活性;用免疫组化方法定量肝组织中α-平滑肌肌动蛋白的表达。结果:与模型组比较,湖北海棠叶总黄酮能够调低血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、透明质酸、羟脯氨酸、β1-转化生长因子含量,降低肝组织丙二醛含量,增加肝组织中总抗氧化能力和总超氧化物歧化酶活性,降低α-平滑肌肌动蛋白的表达;病理学切片显示湖北海棠叶总黄酮能明显减轻CCl4引起的大鼠肝损伤及纤维化程度。结论:湖北海棠叶总黄酮在实验的120mg/kg和60mg/kg两个剂量组对CCl4致大鼠肝纤维化都有防治作用,作用机制可能与其抗氧化作用有关,湖北海棠叶总黄酮能能增强组织抗氧化能力,降低CCl4引起的脂类过氧化,保护细胞膜免受损伤,抑制β1-转化生长因子等具有加重肝纤维化程度的生物因子的表达,减轻肝纤维化程度。     

In vitro and in vivo antioxidant activity of alfalfa (Medicago sativa L.) on carbon tetrachloride intoxicated rats

The present study was conducted to determine whether lyophilized aqueous extract of alfalfa, or Medicago sativa L. could exert antioxidant activity against carbon tetrachloride-induced oxidative stress and liver injury in rats. The hepatoprotective activity of alfalfa extract was determined by assessing the levels of serum transaminases, ALP, bilirubin and lipid profile. Further, the effect of the test substance on malondialdehyde (MDA), an end product of lipid peroxidation; antioxidant liver enzyme non-protein sulfhydryl (NP-SH); and total protein (TP) were also studied. Serum transaminase, ALP, bilirubin level, lipid profile and liver MDA were significantly elevated and the antioxidant status in liver NP-SH and TP contents were declined in animals treated with CCl (4) alone. Pretreatment with alfalfa and silymarin for three weeks prior to the administration of CCl (4) significantly prevented the increase in the serum levels of hepatic marker, LDL, VLDL levels enzymes and reduced oxidative stress indicated by elevated NP-SH and TP concentration. The histopathological examination of the livers also showed that the alfalfa extract reduced the incidence of liver lesions induced by CCl (4). The in vitro antioxidant assessment of alfalfa extract on DPPH and carotene-linoleic assays demonstrated a moderate antioxidant potential. Results suggest that the alfalfa extract possesses hepatoprotective and antioxidative stress properties possibly through its antioxidant phytochemical constituents and substantiates its use in various liver disorders as a hepatoprotector.     

Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats

Astragalosides is the major active constituent of Radix Astragali. The present study was carried out to investigate the effect of crude astragalosides fraction (CAF) on rats liver fibrosis and its possible mechanisms. Hepatic fibrosis was induced by subcutaneous injection with 50% CCl(4) in Sprague-Dawley rats. The amount of CCl(4) administered was 1 mg kg(-1). The alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) were determined with ELISA. Liver samples collected after 8 weeks of CCl(4) treatment were stained with hematoxylin-eosin (HE) and massion, and scored. Intragastric administration of CAF (10, 20 and 40 mg kg(-1)) significantly decreased indices of liver and spleen, the serum transaminase activities, HA and PC III levels, and Hyp and MDA contents in liver tissue in rats of hepatic fibrosis. Decreased SOD and GSH-px levels were reversed after administration of CAF. Histopathological scores showed CAF had inhibitory effect on the progression of hepatic fibrosis. In the in vitro experiments, CAF significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs. The results showed CAF significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of CAF on hepatic fibrosis might be associated with its ability to scavenge free radical and inhibit the production of TNF-alpha and TGF-beta1 from activated KCs.     

化痰行瘀汤对肝纤维化大鼠肝脏超微结构的影响

目的:观察化痰行瘀汤对肝纤维化大鼠肝脏超微结构的影响。方法:60只Wistar大鼠随机分为正常对照组、模型对照组、化痰行瘀汤低、中、高剂量组、复方鳖甲软肝片组6组,每组10只。采用皮下注射四氯化碳(CCl4)橄榄油溶液复制肝纤维化模型,采用透射电镜和扫描电镜观察各组大鼠肝脏的超微结构改变。结果:与模型对照组比较,化痰行瘀汤中、高剂量组大鼠肝细胞、库普弗细胞(KC)、星状细胞(HSC)、内皮细胞超微结构得到明显改善。结论:化痰行瘀汤能减少肝细胞损伤,阻断胶原纤维的生成,而达到抗肝纤维化的目的。     

两种不同治法对肝纤维化大鼠肝组织TGF-β1及其mRNA表达的影响

目的：研究两种不同中药复方对CCl4致肝纤维化大鼠肝组织转化生长因子-β1及mRNA表达的影响,探讨不同中医治法防治肝纤维化的作用机制。方法：皮下注射法制备CCl4大鼠肝纤维化模型,给予两种不同中药复方煎剂灌胃,观察大鼠肝组织匀浆TGF-β1浓度及TGF-β1mRNA表达。结果：与空白对照组比较,模型组大鼠TGF-β1的mRNA和蛋白水平均明显异常表达;治疗1组、2组均可降低肝组织匀浆TGF-β1含量及TGF-β1mRNA表达水平,与模型组比较有显著性差异（P〈0.01或P〈0.05）,尤以滋肾清肝饮组疗效更加明显。结论：滋肾清肝化瘀法与滋肾化瘀法皆可有效防治CCl4大鼠肝纤维化,配伍清热利湿解毒中药后作用可能更加明显。     

Shengmai San reduces hepatic lipids and lipid peroxidation in rats fed on a high-cholesterol diet

Shengmai San (SMS), which is comprised of the medicinal herbs of Panax ginseng C.A. Meyer, Schisandra chinensis Baill., and Ophiopogon japonicus Ker-Gawl (2:1:2)., is a traditional Chinese medicine being used for treating coronary heart disease. The aim of this study was to investigate the effects of SMS on the plasma and liver lipids, lipid peroxidation and antioxidant systems in liver and heart of cholesterol-fed rats. Rats were fed on a high-cholesterol (0.5%) diet (control group), high-cholesterol diet containing 2% SMS (2% SMS group) and 4% SMS (4% SMS group) for four weeks. The oxidative stress marker (thiobarbituric acid reactive substances, TBARS) and antioxidant defense systems including glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities in rat liver and heart were evaluated. Results showed that rats fed with SMS-containing diet had reduced the H(2)O(2)-induced erythrocytes susceptibility to hemolysis, and 4% SMS feeding rats had higher plasma GSH concentration compared to the animals fed with the control diet. However, SMS had no effect on plasma lipids (total cholesterol, triglyceride and high-density lipoprotein cholesterol) and TBARS concentration. On the other hand, rats fed with the 4% SMS diet reduced the hepatic cholesterol and triglyceride contents. Fecal bile acid excretion was significantly increased in rats fed with the SMS-containing diet. Higher hepatic GSH and lower TBARS concentrations were observed in rats fed with the 4% SMS diet compared with the rats fed with the control diet. No significant difference in activities of GSH-Px, GST and SOD was found in liver and heart after the SMS treatment. Results from this study indicate that the SMS may reduce hepatic lipids and lipid peroxidation in rats.     

银杏叶提取物对AFB1诱发大鼠肝癌过程中CYP3A4活性的影响

目的动态观察银杏叶提取物(Ginkgo biloba extract,EGb761)在黄曲霉毒素B1(AFB1)诱发大鼠肝癌过程中对肝组织代谢酶CYP3A4活性的影响。方法将70只4周龄Wistar雄性大鼠随机分为3组:AFB1组(25只),AFB1+EGb761组(25只)及对照组(20只)。在诱发肝癌过程中,分别于第13,23,33,43,53,63周对大鼠进行肝活检;实验至第73周处死全部动物取肝组织;利用大鼠肝组织微粒体混合酶体外代谢体系,采用荧光分光光度定量法动态检测肝标本中CYP3A4酶代谢活性。结果 AFB1+EGb761组肝癌发生率明显低于AFB1组(P<0.01),而对照组为无肿瘤发生。各组肝组织CYP3A4活性在第23周和第53周呈现双波峰变化;AFB1+EGb761组在第53周和第63周时CYP3A4酶活性低于AFB1组,差异有统计学意义(P<0.05)。结论 EGb761可显著降低AFB1诱发大鼠肝癌的发生率。其机制之一可能为抑制大鼠肝组织CYP3A4活性从而减少前致癌物的代谢,降低AFB1致癌性及其化学性肝损伤达到保护肝脏的作用。     

姜黄素抗肝纤维化的实验研究

目的:探讨姜黄素的抗肝纤维化作用。方法:将大鼠随机分为正常对照组、模型组、高、中、低3个剂量姜黄素组和阳性对照组,用皮下注射CC l4法诱导大鼠肝纤维化。测量并计算肝脏指数;测定各组大鼠ALT及AST活性以评价肝功能;同时观察各组大鼠肝脏形态学变化。结果:模型组大鼠肝脏指数均明显低于正常对照组(P<0.01),姜黄素治疗组大鼠肝脏指数明显高于模型组大鼠(P<0.05)。与正常组大鼠比较,模型组大鼠肝脏AST和ALT均显著升高(P<0.01),给予姜黄素治疗后,各治疗组大鼠肝脏AST和ALT活性均显著下降(P<0.05)。HE染色及M asson三色染色显示,秋水仙碱治疗组及各剂量姜黄素治疗组可见肝损伤病变明显减轻,纤维组织增生程度也明显轻于模型组。结论:姜黄素能明显减轻CC l4所致肝损伤,保护肝脏正常结构和功能,延缓肝纤维化。     

益气化瘀化痰养阴方剂对肝纤维化大鼠TGF-β1表达的影响

目的 观察益气化瘀化痰养阴方剂对主要以CCl4诱导的大鼠肝纤维化肝组织TGF-β1表达的影响,探讨益气、化瘀、化痰、养阴单剂与合剂治疗肝纤维化的疗效评价.方法 将130只雄性SD大鼠随机分为正常对照组10只,肝纤维化模型组、益气组、化瘀组、化痰组、养阴组、合剂组各20 只.除正常对照组外,各实验组采用皮下注射四氯化碳+低蛋白高脂饮食+酒精饮料的方法制备肝纤维化模型.模型成功后,根据组别分别灌服生理盐水、益气的黄芪白术饮、化瘀的川芎姜黄饮、化痰的半夏海藻饮、养阴的鳖甲白芍饮和上述8药合煎的具有益气化瘀化痰养阴作用的合剂.于12周末,进行心脏灌注.通过Masson三色胶原染色和电镜以观察肝组织结构的变化,采用RT-PCR及Westem Blot方法观察各组TGF-β1的基因和蛋白表达变化.结果 与肝纤维化模型组相比,益气、化瘀、化痰、养阴单剂均有效降低肝组织内纤维化程度也可以降低大鼠肝组织TGF-β1基因和蛋白表达(P＜0.05).在单剂治疗中,与其它3组相比,益气组疗效最差(P＜0.05),养阴组疗效最好(P＜0.01),化瘀与化痰两组差异不大(P＞0.05).与单剂相比,合剂更能有效降低大鼠肝组织纤维化程度,降低TGF-N基因和蛋白表达(P＜0.05).结论 单剂治疗都可以降低肝组织内纤维化程度,但也有程度差异;合剂更能够明显降低肝组织内纤维化程度,说明益气化瘀化痰养阴法对肝纤维化能达到更好的疗效.     

Effect of schisandrin B and sesamin mixture on CCl(4)-induced hepatic oxidative stress in rats

To study the effects of schisandrin B and sesamin mixture on carbon tetrachloride (CCl(4))-induced hepatic oxidative stress in male Sprague-Dawley rats. The rats were randomly assigned to five groups: control group (olive oil injection), CCl(4) group (CCl(4) injection), silymarin group (CCl(4) injection combined with supplementation of silymarin, 7.5 mg/kg/day), low dose group (CCl(4) injection combined with supplementation of schisandrin B and sesamin mixture at a low dose, 43 mg/kg/day) and high dose group (CCl(4) injection combined with the supplementation of schisandrin B and sesamin mixture at a high dose, 215 mg/kg/day). The hepatic superoxide dismutase and glutathione peroxidase activities of rats in the low dose and high dose groups were increased significantly compared with those in the CCl(4) group. The hepatic reduced glutathione concentration in the silymarin, low dose and high dose groups were increased significantly (48%, 45% and 53%, respectively) when compared with those of the CCl(4) group. In addition, the concentration of glutathione in the erythrocytes of the low dose group was significantly higher than the CCl(4) group by 25%. These results suggest that the schisandrin B-sesamin mixture exerted a hepatoprotective effect by improving the antioxidative capacity in rats under CCl(4)-induced hepatic oxidative stress.