Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats

The hepatoprotective potential of Lygodium flexuosum (L.) Sw. was evaluated in male Wistar rats against carbon tetrachloride-induced liver damage in preventive and curative models. Toxic control and n-hexane extract-treated rats received a single dose of CCl4 (150 microL/100g, 1:1 in corn oil). Pre-treated rats were given n-hexane extracts at 200 and 100 mg/kg dose 48, 24 and 2 h prior to CCl4 administration. In post-treatment groups, rats were treated with n-hexane extract at a dose of 200 and 100 mg/kg, 2, 24 and 48 h after CCl4 intoxication. Rats pre-treated with Lygodium flexuosum remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl4-treated rats. Rats treated with the extract after the establishment of CCl4 induced liver injury showed significant (p < or = 0.05) protection of liver as evidenced from normal AST, ALT, LDH and MDA levels. Hepatic glutathione levels were significantly (p < or = 0.05) increased by the treatment with the extracts in both the experimental groups. Histopathological changes induced by CCl4 were also significantly (p < or = 0.05) reduced by the extract treatment in preventive and curative groups. Phytochemical studies revealed the presence of saponins, triterpenes, sterols and bitter principles in Lygodium flexuosumn-hexane extract which could be responsible for the possible hepatoprotective action.     

Protective effect of Lygodium flexuosum (L.) Sw. (Lygodiaceae) against D-galactosamine induced liver injury in rats

The protective effect of Lygodium flexuosum n-hexane extract against D-galactosamine was evaluated in Wistar rats. In preventive groups extract was administered at 48, 24 and 2h before D-galactosamine intoxication whereas in post-treatment groups extract were administered 2, 24 and 48 h after D-galactosamine intoxication. Rats pre-treated with n-hexane extract at a dose of 200 and 100 mg/kg of Lygodium flexuosum showed a significant prevention of elevated AST, ALT, LDH levels and hepatic malondialdehyde in D-galactosamine treated rats. Hepatic glutathione levels significantly upregulated by the extract treatment in D-galactosamine treated rats. Quantification of histopathological sections supported the preventive action of n-hexane extract of Lygodium flexuosum. Rats treated with the extract at a dose of 200 and 100 mg/kg Lygodium flexuosum after the establishment of D-galactosamine induced liver injury showed complete protection of liver as evidenced from normal AST, ALT and LDH levels, hepatic GSH and MDA levels and also by normal histological index of liver in treated rats. Rats treated with n-hexane extract of Lygodium flexuosum were comparable to that of Silymarin, the standard hepatoprotective drug.     

Protective effects of Ginkgo biloba, Panax ginseng, and Schizandra chinensis extract on liver injury in rats

This study investigated the effects of the combined extracts of Ginkgo biloba, Panax ginseng, and Schizandra chinensis at different doses on hepatic antioxidant status and fibrosis in rats with carbon tetrachloride (CCl4)-induced liver injury. Male Sprague-Dawley rats (n = 8-12 per group) were divided into the control, CCl4, CCl4 + silymarin (0.35%), CCl4 + low-dose herbal extract (0.24% of Ginkgo biloba, Panax ginseng, and Schizandra chinensis extract at 1:1:1; LE), and CCl4 + high-dose herbal extract (1.20% of the same herbal extract; HE) groups. Silymarin or herbal extract was orally given to rats a week before chronic intraperitoneal injection with CCl4 for 6 weeks. The pathological results showed that herbal extract suppressed hepatic bile duct proliferation, and low-dose herbal extract inhibited liver fibrosis. Hepatic superoxide dismutase (SOD) activity was lower in the CCl4 group, but there was no difference in the silymarin or herbal extract treated groups compared to the control group. Hepatic catalase activity and the ratio of reduced to oxidized glutathione were significantly higher (p < 0.05) in the HE group than those in the CCl4 group. Silymarin and herbal extract reversed the impaired hepatic total antioxidant status (p < 0.05). Herbal extract partially reduced the elevated hepatic lipid peroxides. Hepatic transforming growth factor-beta1 (TGF-beta1) level decreased significantly (p < 0.05) in the LE group. Therefore, high-dose herbal extract improved hepatic antioxidant capacity through enhancing catalase activity and glutathione redox status, whereas low-dose herbal extract inhibited liver fibrosis through decreasing hepatic TGF-beta1 level in rats with CCl4-induced liver injury.     

复肝丸对小鼠和大鼠肝纤维化模型的影响

目的:观察复肝丸对四氯化碳诱导的小鼠肝纤维化和二甲基亚硝胺诱导的大鼠肝纤维化的防治作用。方法:小鼠随机分为正常组、模型组、复肝丸组和培哚普利,除正常组外,其余组腹腔注射四氯化碳复制肝纤维化模型;自造模之日起各组灌胃4周。大鼠随机分为正常组、模型组、复肝丸组和培哚普利,除正常组外,其余各组腹腔注射二甲基亚硝胺4周复制肝纤维化模型;造模结束后各组灌胃4周。称重测量肝体比、脾体比,比色法测定血清谷丙转氨酶和谷草转氨酶活性,溴甲酚绿法测定血清白蛋白水平,碱消化法测定肝组织羟脯氨酸含量,HE染色观察肝组织炎性变化、天狼猩红胶原染色观察肝组织病理性胶原沉积变化。结果:与模型组相比,复肝丸10g生药/kg小鼠体重预防用药或6g/kg大鼠体重治疗用药均能降低大鼠和小鼠血清谷丙转氨酶和谷草转氨酶活性,减轻肝脏炎性病理,降低肝组织羟脯氨酸水平,改善肝组织病理性胶原沉积增生。结论:复肝丸对大鼠和小鼠肝纤维化具有防治作用。     

Effect of Ganoderma tsugae on chronically carbon tetrachloride-intoxicated rats

The purpose of this study was to evaluate the hepatoprotective and anti-fibrotic actions of crude extracts of Ganoderma tsugae (GTE) on chronic liver injury induced by carbon tetrachloride (CCl4) in rats. CCl4 (20%, 0.5 ml/rat) was given twice a week for 8 weeks, and animals received GTE through the whole experimental period. GTE showed obvious reducing actions on the elevated levels of glutamate-oxalate-transaminase (GOT) and glutamate-pyruvate-transaminase (GPT) caused by CCl4 at weeks 3, 6 and 8. Liver fibrosis in rats induced by CCl4 led to the drop of serum albumin and hepatic protein concentrations, while GTE increased serum albumin and hepatic protein concentrations. The CCl4-induced liver fibrosis may prolong the prothrombine time and increase albumin/globulin (A/G) ratio. GTE significantly decreased the prothrombine time and A/G ratio. Liver fibrosis induced by CCl4 markedly increased the weight of the spleen, hepatic water and hydroxyproline contents in rats, while GTE decreased the rat's spleen weights, hepatic water and hydroxyproline contents. All these results clearly demonstrated that GTE has hepatoprotective and anti-fibrotic activities.     

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.     

Treatment of chronic liver injuries in mice by oral administration of ethanolic extract of the fruit of Hovenia dulcis

The present study examined the effects of an ethanolic extract of the fruit of Hovenia dulcis (EHD) on chronic hepatitis induced by carbon tetrachloride (CCl(4)) in mice. CCl(4) (5%; 0.1 ml/10 g body weight) was given twice a week for 9 weeks, and mice received EHD throughout the entire experimental period. Plasma activities of GPT and GOT, and hepatic levels of malondialdehyde were significantly lowered in mice treated with EHD as compared to mice treated with CCl(4) only. Histological evaluation showed that EHD could attenuate the liver fibrosis and necrosis caused by CCl(4). RT-qPCR analysis also showed that EHD treatment decreased hepatic collagen (alpha1)(I) and collagen (alpha1)(III) mRNA expressions. Chronic CCl(4) treatment caused liver injuries in mice, characterized by an increase in hepatic methionine adenosyltransferase (MAT) 2A gene expression, and decreased MAT1A gene expression. EHD significantly reduced the changes in MAT gene expression due to the chronic CCl(4) treatment. These results clearly demonstrate that the EHD can reduce hepatic injuries in mice induced by CCl(4).     

Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats

AIM OF THE STUDY: To investigate the protective effects of dehydrocavidine (DC), a main active ingredient of Corydalis saxicola Bunting (Yanhuanglian), on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanisms involved in male Sprague-Dawley rats. MATERIALS AND METHODS: Acute hepatotoxicity was induced by CCl4 intoxication in rats. Serum biological analysis, lipid peroxides and antioxidants estimation, histopathological studies were carried out. RESULTS: Both pre-treatment with DC prior to CCl4 administration and post-treatment with DC after CCl4 administration significantly prevented increases in serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and total bilirubin (TBIL). In addition, pre- and post-treatment with DC also significantly prevented formation of hepatic malondialdehyde (MDA), depletion of glutathione peroxidase (GPx) and depression of superoxide dismutase (SOD) in the liver of CCl4-intoxicated rats. ALT, AST, LDH, ALP and TBILL levels, as well as MDA, SOD and GPx activities were unaffected in normal rats by treatment with DC alone. GST, a phase II enzyme, had no significant changes during our experiments. Histopathological changes induced by CCl4 were also significantly attenuated by DC treatment in both preventive and curative experiments. CONCLUSIONS: DC has a potent hepatoprotective effect on CCl4-induced liver injury in rats through its antioxidant activity.     

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.     

Hepatoprotective effect of Crossostephium chinensis (L.) Makino in rats

The hepatoprotective potential of Crossostephium chinensis (L.) Makino water extract (CCW) on carbon tetrachloride (CCl(4)) induced liver damage was evaluated in preventive and curative rat models. Not only were indicators of hepatic damage including GPT, GOT, lipid peroxides and TBARS were examined, the activities of antioxidant enzymes (SOD, CAT, GPx) and GSH were examined as well. The results showed that CCW (0.1, 0.5 and 1.0 g/kg) significantly reduced the elevated levels of GPT and GOT by CCl(4) administration (p < 0.05). TBARS level was dramatically reduced, and SOD, CAT, GPx and GSH activities were significantly increased. In addition, CCW decreased NO production and TNF-α activation in CCl(4)-treated rats. Therefore, we speculate that CCW protects against acute liver damage through its radical scavenging ability. CCW inhibited the expression of MMP-9 protein, indicating that MMP-9 played an important role in the development of CCl(4)-induced chronic liver damage in rats. In LC-MS-MS analysis, the chromatograms of CCW with good hepatoprotective activities were established. Scopoletin may be an important bioactive compound in CCW.     

Protective effects of total flavonoids of Bidens pilosa L. (TFB) on animal liver injury and liver fibrosis

The hepatoprotective effects of total flavonoids of Bidens pilosa L. (TFB), a traditional Chinese medicine were evaluated in carbon tetrachloride (CCl(4))-induced liver injury in mice and rats. Total flavonoids of Bidens pilosa L. (25, 50 and 100mg/kg) were administered via gavage daily for 10 days to CCl(4)-treated mice as well as TFB (30, 60 and 90mg/kg) administered for 6 weeks to CCl(4)-treated rats. Liver index (liver weight/body weight), serum levels of transaminases (alanine aminotransferase, ALT and aspartate aminotransferase, AST), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated following the 10 days treatment in mice. In addition histopathologic changes and nuclear factor-kappaB (NF-kappaB) expression of the liver were detected with hematoxylin-eosin (HE) and immunohistochemistry methods, respectively. The results showed that TFB (50 and 100mg/kg) effectively reduced the CCl(4)-induced elevated liver index, serum ALT, AST levels, hepatic MDA content, and restored hepatic SOD, GSH-Px activities in acute liver injury mice. TFB (60 and 90mg/kg) treatment significantly inhibited NF-kappaB activation in liver fibrosis of rats. The histopathological analysis suggested that TFB reduced the degree of liver injury in mice and severity of liver fibrosis in rats. These results suggested that TFB had a protective and therapeutic effect on animal liver injury, which might be associated with its antioxidant properties and inhibition of NF-kappaB activation.     

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.     

Hepatoprotective effects of rubiadin, a major constituent of Rubia cordifolia Linn

The hepatoprotective effects of rubiadin, a major constituent isolated from Rubia cordifolia Linn., were evaluated against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Rubiadin at a dose of 50, 100 and 200 mg/kg was administered orally once daily for 14 days. The substantially elevated serum enzymatic activities of serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP) and gamma-glutamyltransferase (gamma-GT) due to carbon tetrachloride treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were also restored towards normalization. In addition, rubiadin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl4 intoxicated rats in a dose dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post treatment against carbon tetrachloride induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that rubiadin has a potent hepatoprotective action against carbon tetrachloride induced hepatic damage in rats.     

Hepatoprotective effects and mechanisms of dehydrocavidine in rats with carbon tetrachloride-induced hepatic fibrosis

Aim of the study

The current study was designed to examine the effects and possible mechanisms of dehydrocavidine (DC) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in male Sprague-Dawley (SD) rats.

Materials and methods

Hepatic fibrosis was induced in male rats with CCl4 administration for 12 weeks. Liver histopathological study was performed, and the liver function was examined by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total bilirubin (TBIL) for evaluating the effect of DC on hepatic fibrosis. The possible mechanisms were investigated by measuring hepatic collagen metabolism and oxidative stress level. Furthermore, oligo microarray analysis of 263 genes was performed, and quantitative real-time RT-PCR was used to verify 4 of the abnormally expressed genes (Bcl2, Cyp3a13, IL18 and Rad50).

Results

DC treatment significantly inhibited the loss of body weight and the increase of liver weight induced by CCl4. DC also improved the liver function of rats as indicated by decreased serum enzymatic activities of ALT, AST, ALP and TBIL. Histopathological results indicated that DC alleviated liver damage and reduced the formation of fibrous septa. Moreover, DC significantly decreased liver hydroxyproline (Hyp) and increased urine Hyp. It also decreased liver malondialdehyde concentration, increased activities of liver superoxide dismutase, catalase and glutathione peroxidase. Microarray analysis revealed that DC altered the expression of genes related to apoptosis, cytokines and other proteins involved in tissue repair.

Conclusions

Our findings indicate that DC can protect rats from CCl4-induced hepatic fibrosis through reducing oxidative stress, promoting collagenolysis, and regulating fibrosis-related genes.     

Hepatoprotective and anti-inflammatory activities of Ballota glandulosissima

Water extract of Ballota glandulosissima Hub.-Mor & Patzak (Lamiaceae) (BG) was investigated for anti-inflammatory activity using the carrageenan-induced rat paw oedema test and for hepatoprotective effect on carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats. Biochemical parameters of hepatic damage such as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin concentrations were determined. CCl(4) (0.8 mL/kg i.p. for 7 days) treatment increased the serum AST, ALT, ALP and bilirubin levels significantly as compared to controls. Treatment of animals with BG (100 mg/kg, i.p.) +CCl(4) (0.8 mL/kg i.p.) for 7 days significantly ameliorated the levels of AST, ALT and ALP elevated by the CCl(4) treatment alone. The results of biochemical tests were also confirmed by histopathological examination. BG together with CCl(4) treatment decreased the balloning degeneration but did not produced apoptosis of hepatocytes, centrilobular and bridging necrosis observed in the CCl(4) treatment alone. BG, at 100 mg/kg per os, showed a significant reduction (34.22%) in rat paw oedema induced by carrageenan. The reference anti-inflammatory drugs etodolac (50 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly reduced the oedeme by 43.42 and 95.70%, respectively. The present study reveals that the water extract of Ballota glandulosissima possesses promising protective activity against CCl(4) induced hepatic damage and anti-inflammatory activity in rats.     

Effect of a urinary preparation on liver injury by short-term carbon tetrachloride treatment in rats.

The hepatoprotective effect of a preparation of human urine (PHU) was assessed against short-term carbon tetrachloride (CCl4) treatment in rats. Significant prevention of liver injury by PHU was found after CCl4 treatment, judging by the changes of serum biochemical parameters, and hepatic protein and triglyceride contents. The increased liver lipid peroxidation, and decreased liver vitamin C concentrations observed after CCl4 treatment were significantly prevented by PHU administration. The increase in liver glutathione (GSH) contents observed after CCl4 treatment was further increased by PHU treatment. Liver catalase activity decreased after CCl4 treatment, while liver superoxide dismutase and GSH-peroxidase activities did not change. PHU administration further inhibited the decrease in liver catalase activity after CCl4 treatment. These results indicate that PHU administration can prevent liver injury induced by CCl4 in rats by inhibiting enhanced lipid peroxidation and by improving disrupted active oxygen metabolism in the injured liver.     

大黄素对大鼠肝纤维化形成的影响

目的；研究大黄素对肝纤维化的影响。方法：采用４０％的四氯化碳（ＣＣｌ４）给予大鼠皮下注射诱导肝纤维化，并以小，中和大剂量大黄素（２０，４０和８０ｍｇ／ｋｇ体重）干预，测定血清透明质酸，层粘连蛋白及肝组织羟脯氨酸，并通过光镜和电镜观察肝组织病理变化。结果：大黄素组较模型组；（１）血清透明质酸及层粘连蛋白显著降低；（２）肝组织胶原蛋白含量明显减少；（３）肝组织纤维化程度明显改善；（４）肝细胞损伤减轻。     

四氯化碳致肝纤维化大鼠模型药理实验方法学研究

目的研究并优化四氯化碳(CCl4)诱导大鼠肝纤维化模型中实验条件。方法在四氯化碳诱导大鼠肝纤维化实验过程中,出现实验大鼠死亡现象;通过控制实验室环境条件和合理处理实验中各种情况,可以很好地减少大鼠死亡,并通过肉眼初步判断大鼠肝纤维化状况。结果选取合理四氯化碳诱导大鼠肝纤维化模型,可以有助于合理地设计肝纤维化实验。结论通过四氯化碳诱导大鼠肝纤维化模型中一般情况阐述,为肝纤维化的基础实验研究及其治疗方案提供参考。     

博落回提取物对实验性肝纤维化的防治作用

目的:观察博落回提取物(Macleaya cordata extract,MCE)对实验性肝纤维化的防治作用.方法:采用CCl4复合因素诱导的大鼠肝纤维化和小鼠血吸虫肝纤维化2种模型,观测MCE干预后肝指数、肝功能生化指标[丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)]、血清纤维化指标[Ⅲ型前胶原( PCⅢ)、层黏连蛋白(LN)、透明质酸(HA))、脂质过氧化指标[谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、超氧化物歧化酶(SOD)),肝组织Ⅰ型胶原(CoⅠ)、Ⅲ型胶原(CoⅢ)及羟脯氨酸(Hyp)表达的变化,并做肝脏病理学检查.结果:在CCl4肝纤维化大鼠模型中,MCE各剂量预防组肝指数,AST含量及CoⅠ表达明显降低,高剂量预防组LN及CoⅢ表达明显降低;中剂量预防组MDA含量及CoⅢ表达明显降低;MCE治疗组肝指数、HA,MDA含量及CoⅢ表达明显降低;经MCE防治后大鼠肝纤维化程度有不同程度减轻.在小鼠血吸虫肝纤维化模型中,MCE预防组小鼠Hyp及Co Ⅰ表达明显降低;高剂量治疗组小鼠肝指数、PCⅢ,LN,HA,AST,ALT含量及Co Ⅰ表达显著降低,中剂量治疗组PCⅢ,HA,AST,ALT含量明显降低;MCE治疗给药能明显改善模型小鼠肝脏病变.结论:MCE对实验性肝纤维化有一定的防治作用,其机制可能与其保护肝细胞膜、减轻肝脏炎症及抗脂质过氧化作用有关.     

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.