Effect of gomisin A (TJN-101), a lignan compound isolated from Schisandra fruits, on liver function in rats

TJN-101 [+)-(6S, 7S, R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy- 6,7-dimethyl-10,11-methylenedioxy-6-dibenzo [a, c] cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. When TJN-101 was administered orally at the doses of 3-100 mg/kg/day for 4 days, bile secretion, hepatic excretion of dye or hepatic hemodynamics 24 hr after the last dose was investigated in comparison with the phenobarbital (100 mg/kg/day)-treated group. Bile flow was dose-dependently increased; in contrast, biliary concentration of bile acids was decreased in TJN-101 (30 and 100 mg/kg/day)-treated groups. Similar changes were also observed in the phenobarbital-treated group. These results suggested that the enhancement of bile secretion caused by TJN-101 or phenobarbital was due to an increase of a bile acid-independent fraction. In the bromosulfophthalein (BSP) clearance test for liver function, both TJN-101 (30 and 100 mg/kg/day) and phenobarbital accelerated the disappearance from the blood and biliary excretion of BSP. Hepatic hemodynamics was examined by the hydrogen clearance method and measurement of liver wet and dry weight. Liver blood flow tended to increase in the TJN-101 (10-100 mg/kg/day) or phenobarbital-treated group. On the other hand, TJN-101 (3-100 mg/kg/day) or phenobarbital hardly altered the water content of the liver. These results suggested that the liver enlargement caused by both compounds was not accompanied with hepatic edema and that the enhancement of bile secretion or hepatic excretion of BSP might be related to an increase of liver blood flow.     

Effects of cianidanol on chronic liver injury induced by carbon tetrachloride and on liver regeneration after partial hepatectomy in rats

Effects of cianidanol on chronic liver injury induced by prolonged administration of carbon tetrachloride (CCl4) and on liver regeneration after partial hepatectomy of normal liver and CCl4 chronically injured liver were investigated by the measurement of plasma and liver biochemical parameters. Cianidanol increased the total plasma protein and 14C-Leu incorporation into plasma protein, while it reduced the contents of liver cholesterol and triglycerides. In rats with chronically injured liver or regenerating liver after partial hepatectomy of chronically injured liver, cianidanol improved the retention rate of BSP and the content of liver sugar. In rats with chronically injured liver, plasma GPT and GOT activities were reduced with the administration of cianidanol. Cianidanol had no effect on the regeneration rate after partial hepatectomy of normal liver, but it increased the regeneration rate after partial hepatectomy of chronically injured liver. These results suggest that cianidanol has the effect of improving the function of liver cells damaged by CCl4 treatment and of promoting the recovery of cell function to a normal level.     

Deferoxamine alleviates liver fibrosis induced by CCl4 in rats

Several chronic liver diseases can lead to the occurrence of hepatic fibrosis through the accumulation of iron, which causes induction of oxidative stress and consequently activation of fibrogenesis. The present study was designed to investigate the potential antifibrotic and anti‐oxidant effects of deferoxamine (DFO), a well‐known iron chelator in an experimental rat model of liver injury using carbon tetrachloride (CCl₄). First, the potential effective dose of DFO was screened against CCl₄‐induced acute hepatotoxicity. Then, rats were co‐treated with DFO (300 mg/kg, i.p.) for 6 weeks starting from the third week of CCl₄ induction of chronic hepatotoxicity. Liver function was assessed in addition to histopathological examination. Furthermore, oxidative stress and fibrosis markers were assessed. It was found that treatment of animals with DFO significantly counteracted the changes in liver function; histopathological lesions and hepatic iron deposition that were induced by CCl₄. DFO also significantly counteracted the CCl₄‐induced lipid peroxidation increase and reduction in antioxidant activities of superoxide dismutase and glutathione peroxidase enzymes. In addition, DFO ameliorated significantly liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cells (HSCs) activation marker; alpha smooth muscle actin and transforming growth factor‐beta (TGF‐β). Together, these findings indicate that DFO possesses a potent antifibrotic effect due to its antioxidant properties that counteracted oxidative stress and lipid peroxidation and restored antioxidant enzymes activities as well as reducing HSCs activation and fibrogenesis.     

异甘草酸镁对大鼠四氯化碳慢性肝损伤的治疗作用

目的 :观察异甘草酸镁 (MgIG )治疗大鼠慢性四氯化碳 (CCl4 )肝损伤的疗效。方法 :12 0只SD大鼠随机分成正常对照组 ,模型对照组 ,阳性对照组和MgIG 15 ,30 ,6 0mg·kg- 1治疗组 6组。除正常对照组外 ,所有动物皮下注射 2 5 %CCl4 橄榄油液 2mL·kg- 1,每周 2次 ,连续 13wk。wk 5起 ,相应予生理盐水 ,生理盐水 ,复方甘草甜素注射液 ,MgIG 15 ,30 ,6 0mg·kg- 1,ip ,qd ,连续至 13wk。结果 :与模型对照组相比 ,MgIG能显著降低慢性CCl4肝损伤大鼠血清转氨酶、唾液酸、透明质酸以及血浆一氧化氮、肝组织羟脯氨酸含量 ,且呈剂量依赖性。另外 ,MgIG可减轻肝组织炎症及纤维化。结论 :MgIG对大鼠CCl4 慢性肝损伤具有治疗作用     

Therapeutic effect of TRQ on chronic liver injury model in rats induced by CCl4

Rats were treated with CCl4 for 12 weeks to induce chronic liver injury. An administration of tritoqualine (TRQ) to rats was begun 3 weeks after the first CCl4 treatment, and the therapeutic effect of TRQ on this model was investigated. On the 12th week after CCl4 treatment, a marked increase in content of hydroxyproline and histamine in the liver was found. In addition, increased fibrosis around Glisson's sheath was observed under microscopic observation. The increase in these biochemical parameters was suppressed significantly in the rats administered TRQ at doses of 25-100 mg/kg. The histopathological observation demonstrated the suppression of the formation of pseudolobules with fibrinogenesis in the liver of TRQ administered rats. In addition, there was a noticeable improvement in the activity of the liver protein synthesis in the TRQ administered rats when the parameters that represented the hepatic functions were measured. Glutamic oxaloacetic transaminase in the serum of TRQ-administered rats also decreased significantly, compared with the CCl4 treated control rats. From these results, TRQ was shown to exhibit a marked therapeutic effect on liver damage accompanied by chronically accelerated fibrosis in rats which have been treated with CCl4 for 12 weeks.     

Effect of tritoqualine on liver regeneration after partial hepatectomy in rats

Effect of tritoqualine (TRQ) on liver regeneration after partial hepatectomy in normal rats and chronically injured rats treated with carbon tetrachloride (CCl4) for 12 weeks were investigated by the measurement of serum and liver biochemical parameters concerning the hepatic function. The results are as follows: 1) In normal rats, the liver regeneration rate after partial hepatectomy was increased dose-dependently with the administration of TRQ for 7 days after the operation. TRQ improved BSP retention rate which was decreased after partial hepatectomy. In addition, protein synthetic activity in the liver microsomes prepared from TRQ-administered rats was higher than that prepared from control rats, and the contents of serum total protein, serum albumin and liver protein were also higher in TRQ-administered rats. 2) In the rats treated with CCl4 for 12 weeks, the liver regeneration rate after partial hepatectomy was increased dose-dependently with the administration of TRQ for 6 days. TRQ also improved the contents of serum total protein, serum albumin and liver protein. Though the amount of collagen in the liver chronically injured by CCl4 increased more than twice compared with that in the normal liver, the amount of collagen in the regenerating liver of CCl4-treated rats whose liver regeneration was accelerated by TRQ was not different from that in the normal liver. These results suggest that TRQ has the effect of improving the various hepatic functions through the activation of the protein synthesis in hepatocytes.     

肝舒胶囊对CCl4致大鼠慢性肝损伤的影响

目的 研究肝舒胶囊对大鼠慢性肝损伤的保护作用.方法 采用sc CCl4致大鼠慢性肝损伤,比色法测定血清中的ALT、AST、ALP、TP、ALB的含量,碱水解法测定肝组织中羟脯氨酸(HYP)的含量,并根据肝脏的脂变、炎症、水肿、细胞坏死、纤维组织增生观察病理组织学的形态变化.结果 肝舒胶囊对血清中生化指标有一定的降低趋势,可明显降低血清中ALP和肝组织中的HYP;可明显改善肝组织的病理学变化.结论 肝舒胶囊对慢性肝损伤有一定的保护作用.     

重组人红细胞生成素对大鼠肝切除后肝再生的影响

目的 探讨重组人红细胞生成素(rhEPO)对大鼠肝切除后肝再生的促进作用.方法 大鼠建立70%肝切除模型后分为两组:实验组术后30 min经尾静脉注射累计4000 IU/kg rhEPO(每天1333 IU/kg rhEPO,连用3 d);对照组给予相同容量的生理盐水.术后1、3、5、7、14 d随机各取5只大鼠处死,称取并计算肝再生率,采用速率法检测血清丙氨酸转氨酶(ALT)和白蛋白(Alb),免疫组化检测肝组织增殖细胞核抗原(PCNA)表达.结果 术后1、3、5、7、14 d实验组肝再生率较实验组明显增高(P＜0.05),实验组血清ALT水平术后5、7、14 d较对照组有降低(P＜0.05),实验组血清Alb术后7、14 d高于对照组(P＜0.05),术后1、3、5、7 d实验组PCNA标记指数均高于对照组(P＜0.05和P＜0.01).结论 rhEPO对大鼠肝切除后肝再生有促进作用.     

Effects of bemethyl, ethomersol, and yakton on the liver regeneration after partial hepatectomy

It is experimentally demonstrated for the first time that the new drugs bemithyl, etomerzol, and yakton are capable of accelerating the process of liver regeneration following partial hepatectomy. The drugs produce a hasty gain in the mass of liver, increase in the content of nucleic acids and glycogen, and improve the functional state, as manifested by a decrease in the blood bilirubin and a reduction in the hexenal sleep duration. Bemithyl, etomerzol, and yakton produce a positive effect upon the liver morphology and the intracellular regeneration process. The repair activity of the new drugs exceeds that of a combination of the well-known regeneration stimulants riboxin and potassium orotate, representing derivatives of purine and pyrimidine bases.     

扶正化瘀方对大鼠肝大部切除后肝再生的影响

目的 探讨扶正化瘀方对大鼠肝大部切除(PH)后肝再生的影响.方法 将28只正常雄性Wistar大鼠随机分为4组,分别为假手术组(对照组)、PH模型(PH)组、PH+扶正化瘀组和PH+促肝细胞生长素(pHGF)组,每组7只.扶正化瘀组和PH +pHGF组于实验前3天至实验结束,分别给予扶正化瘀方药液灌胃1 ml/l00 g和pHGF腹腔注射1 ml/100 g,每日1次.术后24 h心脏采血后处死大鼠,计算各组肝再生速度,血清标本检测ALT、AST、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平,免疫组织化学染色和荧光定量PCR检测肝组织cyclinD1的表达.结果 PH组、PH +pHGF组和PH+扶正化瘀组ALT、AST水平明显升高,白蛋白水平明显下降,与对照组比较差异均有统计学意义(均P ＜0.01).与对照组比较,PH组、PH +pHGF组和PH+扶正化瘀组血清TNF-α和IL-6水平均明显升高(均P＜0.01).与对照组比较,PH组、PH+扶正化瘀组和PH +pHGF组大鼠有丝分裂指数、肝组织cyclin D1 mRNA和肝细胞核cyclin D1阳性率均明显升高(均P＜0.01);PH+ PHGF组和PH+扶正化瘀组肝再生速度明显高于PH组[(22±4)％、(20±2)％比(13±1)％,P＜0.01].与对照组比较,PH组、PH +pHGF组和PH+扶正化瘀组有丝分裂指数、肝组织cyclinD1 mRNA和肝细胞核cyclin D1阳性率均明显升高[有丝分裂指数:(25.90±0.95),(29.70±0.50),(30.30±0.96)％比(0.95±0.19)％;肝组织cyclin D1 mRNA:2.18±0.37,2.73±0.29,2.93±0.18比1.03±0.09;肝细胞核cyclin D1阳性率:(27.20±0.36)％,(28.30±0.16)％,(29.30±0.21)％比(0.95±0.19)％](P＜0.01或P＜0.05),而PH+扶正化瘀组和PH +pHGF组间差异无统计学意义(P＞0.05).结论 扶正化瘀方可通过增强cyclinD1表达而促进大鼠肝大部切除术后的肝再生.     

青蒿琥酯抗四氯化碳致大鼠肝纤维化的作用

青蒿素类主要用于治疗疟疾,对矽肺、烧伤后增生性瘢痕也有防治作用[1,2],尚未见其抗肝纤维化的报道.本研究采用CCl4 诱发大鼠肝纤维化模型,观察青蒿琥酯(Artesunate)的作用.     

五味子藤茎中木脂素对四氯化碳致小鼠急性肝损伤的保护作用

目的：探讨五味子藤茎中木脂素对四氯化碳（CCl4）致小鼠急性肝损伤的保护作用。方法：采用CCl4致小鼠急性肝损伤模型,观察五味子藤茎中木脂素对小鼠血清ALT、AST活性及肝组织匀浆超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）水平的影响,同时观察肝组织病理学改变。结果：五味子藤茎中木脂素能明显降低血清ALT、AST水平,降低肝匀浆MDA的含量,提高SOD、GSH-Px活力,肝脏病理损伤有明显改善。高剂量组抗肝损伤作用与联苯双酯阳性对照组相当。结论：五味子藤茎中木脂素对CCl4致小鼠急性肝损伤具有一定的保护作用,其作用机制与其抗氧化作用有关。     

A comparative study of human placenta hydrolysate (Laennec) by intravenous or subcutaneous injection on liver regeneration after partial hepatectomy in normal and CCl4-induced cirrhosis rats

The effect of human placenta hydrolysate (Laennec) on residual liver regeneration after about 70% partial hepatectomy (PH) in normal and CCl4-induced cirrhosis rats was examined. Both intravenous or subcutaneous injections of Laennec increased the regeneration rate of the residual liver after PH in normal rats. Intravenous injection of Laennec inhibited the decrease of liver total protein, and it decreased the level of serum transaminase (GOT, GPT). The regeneration rate of the residual liver after PH in CCl4-induced cirrhosis (CCl4-PH) rats increased by intravenous or subcutaneous injection of Laennec. Laennec also inhibited the increase of serum GOT caused by CCl4-PH. In the pathological examination of the regenerating liver, intravenous injection of Laennec minimized the pathological changes caused by PH or CCl4-PH such as vacuolation and necrosis in the hepatocytes. The enhancement of cytoplasma regeneration in hepatocytes was noticed by intravenous injection of Laennec, but that by subcutaneous Laennec was slight. Intravenous injection of Laennec also minimized the lipid deposition in liver caused by CCl4-PH. Laennec had no effect on the pseudolobule formation caused by CCl4. Thus, the effect of intravenous injection of Laennec on the liver regeneration in PH rats was much more potent than that by the subcutaneous injection.     

丹酚酸A抗四氯化碳中毒致大鼠肝损伤和肝纤维化的作用

目的：研究丹酚酸Ａ（ＳＡＡ）抗肝损伤、肝纤维化作用．方法：采用ＣＣｌ４诱导大鼠肝损伤及肝纤维化，期间予ＳＡＡ灌胃治疗，另设秋水仙碱（Ｃｏｌ）组、丹参组作对照，６周后进行肝组织病理学和Ⅰ、Ⅲ型胶原免疫组化观察，肝组织羟脯氨酸（Ｈｙｄ）、丙二醛（ＭＤＡ）含量及血清ＡｌａＡＴ、ＡｓｐＡＴ和白蛋白含量测定．结果：ＳＡＡ降低血清ＡｌａＡＴ、ＡｓｐＡＴ水平及肝组织ＭＤＡ、Ｈｙｄ含量，减轻肝纤维化程度，抑制Ⅰ、Ⅲ型胶原在基质中沉积．其抗肝纤维化强度与Ｃｏｌ、丹参一致，对ＭＤＡ作用优于Ｃｏｌ．结论：ＳＡＡ有显著的抗肝损伤、肝纤维化作用，与抗脂质过氧化有关     

丹参素和泮托拉唑对肝硬化大鼠肝部分切除术后肝再生的影响研究

目的以肝硬化大鼠为动物模型,研究药物对肝硬化大鼠肝部分切除术后肝再生的影响。方法取健康的Wistar雄性大鼠64只,以60%CCl4油溶液0.3ml/100g皮下注射,同时饮用5%酒精溶液,45d后制成肝硬化动物模型。模型大鼠随机分为4组,16只/组。全麻下均行左、中叶肝切除术。术后各组按以下方案处理:对照组皮下注射生理盐水1mg·kg-1·d-1,丹参素组腹腔注射18mg·kg-1·d-1,泮托拉唑组皮下注射0.2mg·kg-1·d-1,两药合用组同时给予丹参素(tanshinol)腹腔注射18mg·kg-1·d-1,泮托拉唑(pantoprazole)皮下注射0.2mg·kg-1·d-1,连续给药2周,抽取静脉血样,取肝脏组织,检测肝功能、有丝分裂指数(MI)、增生细胞核抗原(PCNA)、细胞核DNA含量。结果丹参素组、泮托拉唑组及两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于对照组(P<0.05),两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于丹参素组、泮托拉唑组(P<0.05),但各组间肝功能变化无明显差异。结论丹参素、泮托拉唑及两药合用均对肝硬化大鼠肝部分切除术后肝细胞再生有促进作用。     

Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats

AIM: To study the effect of leflunomide on CC14-induced hepatic fibrosis in rats. METHODS: Hepatic fibrosis was induced by subcutaneous injection with 50 % CCl4 in Sprague-Dawley rats. The amount of CC14 administered was 1 mg/kg. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. The transforming growth factor-β1(TGF-β1) in serum was determined by ELISA. The nuclear factor-kappa B (NF-κB) in liver tissue was examined by immunohistochemistry. Liver samples collected after 12 weeks ofCC14 treatment were stained with hematoxy-lin and eosin. RESULTS: Leflunomide (1, 3, and 9 mg/kg) significantly decreased indices of liver and spleen, the serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological examination showed leflunomide had inhibitory effect on fibrogenesis and formation of pseudolobulus. Furthermore, leflunomide significantly inhibited NF-κB expression in liver tissue, and reduced elevated serum TGF-κB and NO levels in rats of hepatic fibrosis. CONCLUSION: Leflunomide showed inhibitory action on hepatic fibrosis induced by CC14 in rats.     

丹酚酸A抗四氯化碳中毒致大鼠肝损伤和肝纤维化的作用

目的：研究丹酚酸Ａ（ＳＡ－Ａ）抗肝损伤、肝纤维化作用。方法：采用ＣＣｌ４诱导大鼠肝损伤及肝纤维化，期间予ＳＡ－Ａ灌胃治疗，另设秋水仙碱（Ｃｏｌ）组、丹参组作对照，６周后进行肝组织病理学和Ｉ、Ⅲ型胶原免疫组化观察，肝组织羟脯氨酸（Ｈｙｄ）、丙二醛（ＭＤＡ）含量及血清ＡｌａＡＴ、ＡｓｐＡＴ和白蛋白含量测定。结果：ＳＡ－Ａ降低血清ＡｌａＡＴ、ＡｓｐＡＴ水平及肝组织ＭＤＡ、Ｈｙｄ含量，减轻肝纤维化程度，抑     

苯丙氨酸二肽类化合物Y101对CCl_4诱导大鼠慢性肝损伤的保护作用

目的:观察苯丙氨酸二肽类化合物Y101对CC l4诱导大鼠慢性肝损伤的保肝作用,探讨其作用机制。方法:CC l4加苯巴比妥诱导大鼠慢性肝损伤,实验分正常组、模型组、Y101低、中、高剂量组(17.5,35,70 m.gkg-1),阳性对照组(鳖甲软肝片,540 m.gkg-1),分别进行防治和给药,7周疗程结束后处死大鼠,检测其血清中谷丙转氨酶(ALT),谷草转氨酶(AST),碱性磷酸酶(ALP)的活性及白蛋白(ALB),总蛋白(TP)含量。取肝脏,称重,检测肝脏中羟脯氨酸(HyP),丙二醛(MDA),一氧化氮(NO),超氧化物歧化酶(SOD),谷胱甘肽(GSH)的含量;另取肝脏做病理组织学检查,取脾、胸腺,称重,将所得数据进行统计分析。结果:与正常组比较,模型组大鼠血清中ALT,AST,ALP活性,肝内HyP,MDA,NO含量及胸腺重量显著升高(P<0.01),血清中ALB,TP含量,肝内SOD,GSH水平及肝脾重量明显降低(P<0.01)。低、中、高剂量Y101对慢性肝损伤大鼠上述指标均有不同程度的改变,且呈良好的剂量关系。给予Y101治疗后,中、高剂量组的肝组织病理变化均明显轻于模型组。结论:Y101对...