Ductular reaction at the early terms of common bile duct ligation in the rats

Ductular reaction (DR) in bile duct ligated rats generally appears from 2nd day after biliary obstruction (BO). However, we show that increased amount of ductular profiles is evident already in 6 hours after BDL. The study aims to explain the origin of such an early DR in response to BO. Male Lewis rats were subjected to common bile duct ligation (CBDL) for 3, 6, 12 and 24 hours and sham operation. Liver samples were studied histologically, immunohistochemically (Ki67, pan-Cytokeratin /AE1 + AE3/ and OV-6) and by immunoblotting analyses. It appeared that number of ductular profiles increase in time-related manner after BO. These ductular profiles are formed by biliary epitheliocyte-like cells; No mitotic activity was revealed. Part of hepatocytes reveals pan-Cytokeratin positivity on 12 and 24 hours after BO. Total cytokeratins content at 24 hours after CBDL was 37% higher in comparison with control data. The significant increase was observed for the cytokeratins with molecular weights: 61, 56 and 40 KDa. Thus, early DR after BDL is mediated by widening of the existed finest biliary ramifications and is not associated with proliferation activities. This DR is accompanied by differentiation of hepatocytes toward bile duct-like cells.     

Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents

Organic solute transporter (OSTalpha-OSTbeta) is a novel heteromeric bile acid and sterol transporter expressed at the basolateral membranes of epithelium in the ileum, kidney, and liver. To determine whether OSTalpha-OSTbeta undergoes farnesoid X receptor (FXR)-dependent adaptive regulation following cholestatic liver injury, mRNA and protein expression levels were analyzed in patients with primary biliary cirrhosis (PBC) and following common bile duct ligation (CBDL) in rats and Fxr null and wild-type mice. Hepatic OSTalpha and OSTbeta mRNA increased 3- and 32-fold, respectively, in patients with PBC compared with controls, whereas expression of Ostalpha and Ostbeta also increased in the liver of rats and mice following CBDL. In contrast, expression of Ostalpha and Ostbeta mRNA was generally lower in Fxr null mice, and CBDL failed to enhance expression of Ostalpha and Ostbeta compared with wild-type mice. HepG2 cells treated for 24 h with chenodeoxycholic acid, a selective FXR ligand, had higher levels of OSTalpha and OSTbeta mRNA and protein. Increases in OST protein were visualized by confocal microscopy at the plasma membrane. These results indicate that expression of Ostalpha and Ostbeta are highly regulated in response to cholestasis and that this response is dependent on the FXR bile acid receptor.     

TNF-alpha and leptin in experimental liver fibrosis models induced by carbon tetrachloride and by common bile duct ligation

In this study we investigated TNF-alpha and leptin levels in two different liver fibrosis models induced by carbon tetrachloride (CCl(4)) and common bile duct ligation (CBDL). A total of 36 male rats of Albino-Wistar strain were allocated to three groups. One of the groups was the control. The second group received 0.15 ml 100 g(-1) CCl(4) subcutaneously for 6 weeks, 3 days per week. The third group underwent common bile duct ligation (CBDL) and was monitored for 4 weeks. Histopathological investigation included fibrosis, steatosis and inflammation. Serum IL-6 and TNF-alpha levels were analysed by ELISA methods and leptin was analysed by RIA. Fibrosis and steatosis increased significantly in the CCl(4) group in comparison with the CBDL group (p < 0.01; p < 0.001). Leptin and TNF-alpha levels in CCl(4) group were higher than those in the CBDL and control groups (p < 0.05). TNF-alpha and leptin levels were not related to each another in either the CCl(4) group or the CBDL group (r=0.22, p > 0.05; r=0.19, p > 0.05). The IL-6 level was higher in the CCl(4) group in relation to severity of inflammation (p < 0.05). TNF-alpha and leptin levels were higher in animals with liver fibrosis induced by CCl(4), than they were in those whose liver fibrosis was induced by common bile duct ligation. Leptin and TNF-alpha may be less effective on the development of liver fibrosis in the group which underwent common bile duct ligation.     

The effects of Nigella sativa on bile duct ligation induced‐liver injury in rats

Nigella sativa (NS) has been shown to have antioxidant and antiinflammatory activities in different conditions. The goal of this study was to evaluate the effects of NS on cholestatic liver injury in rats. Thirty rats were recruited in the study as follows: Group 1, Bile duct ligation (BDL) (n = 10); Group 2, BDL plus NS (n = 10); and Group 3, Sham (n = 10). Bile duct ligated group received 0.2 mL kg^?1 dose of NS intraperitoneally daily throughout 14 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. Data showed a decrease in gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities of the NS treated rats when compared with BDL group (p < 0.001 for GGT and p < 0.05 for others). The NS treated rats' tissue levels of total oxidant status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) were significantly lower than that of the BDL group (p < 0.01 for all). Increases in total antioxidant capacity (TAC) and catalase (CAT) levels were statistically significant in the NS treated rats compared to BDL group (p < 0.01 for both). On the other hand, administration of NS in the rats with biliary obstruction resulted in inhibition of necro‐inflammation. These results indicate that NS exerts a therapeutic effect on cholestatic liver injury in bile duct ligated rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. Copyright © 2009 John Wiley & Sons, Ltd.     

Viability and plasma vitamin K levels in the common bile duct-ligated rats.

The common bile duct-ligated (CBDL) rat, which is widely used as a model of human cirrhosis, rapidly develops secondary biliary cirrhosis (SBC) within 4 weeks. The CBDL rat shows poor viability, however, a detailed examination of the causes of its death has not been made. In this study, we investigated the outcome of bile duct ligation in detail and attempted to extend the life span of this model by feeding the animals a diet supplemented with nutrients. Survival rate, blood chemistry, blood cell counts, plasma levels of K vitamins and liver histology were compared among CBDL rats fed a standard diet and an enriched diet. Sham-operated rats were used as a control. Six out of 18 CBDL rats fed the standard diet died within 32 days of operation. The cause of death was massive internal hemorrhage in various organs or body cavities. All CBDL rats fed the enriched diet survived more than 31 days, but the viability of CBDL rats was not significant between those fed the standard diet and the enriched diet. The degree of anemia correlated significantly with the prolongation of prothrombin time. Plasma vitamin K1 levels in CBDL rats were significantly lower than those in sham-operated rats, but vitamin K2 levels were similar. We suggest that massive hemorrhage, which was the direct cause of death, is caused by the impairment of hemostasis resulting from vitamin K deficiency. The enriched diet with vitamin K nutritional supplements seemed to contribute to the prolongation of the life span of CBDL rats.     

Protective effects of thymoquinone against cholestatic oxidative stress and hepatic damage after biliary obstruction in rats

The aim of this study was to examine the preventive and therapeutic effects of thymoquinone (TQ) against cholestatic oxidative stress and liver damage in common bile duct ligated rats. A total of 24 male Sprague–Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received TQ; each group contain 8 animals. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally for 2 weeks starting 3 days prior to BDL operation. To date, no more biochemical and histopathological changes on common bile duct ligated rats by TQ treatment have been reported. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GPx)] activities. TQ treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with TQ attenuated alterations in liver histology. The immunopositivity of alpha smooth muscle actin and proliferating cell nuclear antigen in BDL were observed to be reduced with the TQ treatment. The present study demonstrates that oral administration of TQ in bile duct ligated rats maintained antioxidant defenses and reduces liver oxidative damage and ductular proliferation. This effect of TQ may be useful in the preservation of liver function in cholestasis.     

ET-1 and TNF-alpha in HPS: analysis in prehepatic portal hypertension and biliary and nonbiliary cirrhosis in rats

Common bile duct ligation (CBDL) triggers a molecular cascade resulting in the hepatopulmonary syndrome (HPS). Both increased hepatic endothelin-1 (ET-1) production and pulmonary vascular ET(B) receptor expression with stimulation of endothelial nitric oxide synthase and TNF-alpha mediated inducible nitric oxide synthase and heme oxygenase-1 expression in pulmonary intravascular macrophages occur. Whether biliary cirrhosis is unique in triggering ET-1 and TNF-alpha alterations and HPS is unknown. We evaluated for HPS in rat prehepatic portal hypertension [partial portal vein ligation (PVL)], biliary (CBDL) and nonbiliary [thioacetamide treatment (TAA)] cirrhosis, and assessed ET-1 infusion in normal and PVL animals. Control, PVL, CBDL, TAA-treated, and ET-1-infused PVL animals had ET-1 and TNF-alpha levels measured and underwent molecular and physiological evaluation for HPS. HPS developed only in biliary cirrhosis in association with increased plasma ET-1 and TNF-alpha levels and the development of established molecular changes in the pulmonary microvasculature. In contrast, PVL did not increase ET-1 or TNF-alpha levels and TAA treatment increased TNF-alpha levels alone, and neither resulted in the full development of molecular or physiological changes of HPS despite portal pressure increases similar to those after CBDL. Exogenous ET-1 increased TNF-alpha levels and triggered HPS after PVL. Combination of ET-1 and TNF-alpha overproduction is unique to biliary cirrhosis and associated with experimental HPS. ET-1 infusion increases TNF-alpha levels and triggers HPS in prehepatic portal hypertension. ET-1 and TNF-alpha interact to trigger pulmonary microvascular changes in experimental HPS.     

Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats

BACKGROUND: Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. OBJECTIVE: The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). METHODS: Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples. RESULTS: In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. CONCLUSION: Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.     

Alkaline phosphatase in cholestatic and cirrhotic rats. A biochemical and histochemical study

Alkaline phosphatase (ALP) was studied by enzyme histochemical methods and by biochemical quantitations in rat livers with chronic bile duct obstruction and experimental cirrhosis. The most evident ALP increase was histochemically found in portal tracts of rats with bile duct obstruction and localized to the walls of proliferating blood vessels. Furthermore, a slight canalicular membrane enzyme increase was histochemically found in both groups, most evident in cirrhosis, whereas the biochemical assay of ALP in serum and liver from both pathological groups showed 3 times higher values compared to controls. The portal tracts did not seem to contribute to the serum increase, since the rise of serum ALP was similar in chronic bile duct obstruction and in experimental cirrhosis without changes of the portal tracts. It is concluded that the increase ALP activity in serum from rats with bile duct obstruction and cirrhosis mainly has a hepatocytic origin.     

Interleukin-6 (IL-6) and acute-phase proteins in rats with biliary sepsis.

We measured serum interleukin-6 (IL-6) and acute-phase proteins, alpha 1-acid glycoprotein (AGP) and alpha 2-macroglobulin (alpha 2M), after a retrograde intrabiliary bacterial infection in rats with biliary obstruction. Maximum serum IL-6 was obtained at 6 h in rats following inoculation of bacteria (10(6) CFU/ml E. Coli) in the bile duct and it was higher than that observed in rats undergoing a bile duct ligation or a laparotomy. There was a strict relationship between the level of IL-6 at 6 h and the modified levels of AGP and alpha 2M at 48 h. AGP and alpha 2M levels were the highest in sera of rats with bile duct infection as compared with those found in sera of rats with bile duct ligation or laparotomy. After inoculation of E. Coli or E. Fecalis, blood IL-6 level was always higher at 6 h in inferior vena cava as compared with that found in the supra hepatic vein. These results indicate that IL-6 is synthesized after a biliary sepsis and that its blood level is higher in the systemic circulation than in the local circulation.     

The various impacts of the hepatitis C virus core protein upon hepatic oxidative stress after common bile duct ligation and partial hepatectomy

Abstract

Introduction: Although it is uncertain how the hepatitis C virus (HCV) core protein influences hepatic oxidative stress after partial hepatectomy and common bile duct ligation (CBDL) this may be crucial for the prognosis of patients with HCV infection who have undergone hepatic resection, or who have complications due to a biliary tract obstruction.

Materials and methods: A group of double transgenic mice (DTM) that express both the tetracycline transactivator (tTA) and the HCV core, with conditional, acute expression of the HCV core in the context of the mature liver were subjected to 43% partial hepatectomy and CBDL. The levels of thioredoxin-1, thiobarbituric acid reactive substances (TBARS), and 4-hydroxynonenal (4-HNE) were evaluated in liver samples taken 3 days after the operations.

Results: The DTM had significantly higher TBARS levels than mice that were transgenic for only tTA (i.e. single transgenic mice; STM) and non-transgenic mice (NTM) after a sham laparotomy, CBDL and partial hepatectomy. Of the DTM, the TBARS levels were higher in female mice than in males after a sham laparotomy (P = 0.02) and CBDL (P = 0.0001). 4-HNE staining data were compatible with these results. Furthermore, male DTM exhibited higher levels of thioredoxin-1 than female DTM after sham laparotomy (P = 0.012) and CBDL (P = 0.008).

Conclusions: The HCV core increases hepatic oxidative stress in vivo and female DTM are more vulnerable to the oxidative stress caused by acute core expression with, or without, CBDL. The fact that the female DTM had lower thioredoxin-1 levels may account for this observation.     

Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL+BBS (10 μg/kg, s.c. ×3), BDL+NT (300 μg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.     

Long-term administration of aqueous garlic extract (AGE) alleviates liver fibrosis and oxidative damage induced by biliary obstruction in rats

The aim of this study was to assess the antioxidant and antifibrotic effects of chronic administration of aqueous garlic extract on liver fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). Aqueous garlic extract (AGE, 1 ml/kg, i.p., corresponding to 250 mg/kg) or saline was administered for 28 days. At the end of the experiment, rats were killed by decapitation. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver functions and tissue damage, respectively. Tumor necrosis factor-alpha (TNF-alpha) was also assayed in serum samples. Liver tissues were taken for determination of the free radicals, renal malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker was also determined. Serum AST, ALT, LDH, and TNF- alpha levels were elevated in the BDL group as compared to control group, while this increase was significantly decreased by AGE treatment. Hepatic GSH levels, significantly depressed by BDL, were elevated back to control levels in AGE-treated BDL group. Increases in tissue free radical and MDA levels and MPO activity due to BDL were reduced back to control levels by AGE treatment. Similarly, increased hepatic collagen content in the BDL rats was reduced to the level of the control group with AGE treatment. Since AGE administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic structure and function, it seems likely that AGE with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.     

Factors influencing the inhibition of biliary glutathione efflux induced by biliary obstruction

The aim of this study was to investigate mechanisms responsible for the inhibition of biliary glutathione efflux in rats with secondary biliary cirrhosis. Rats were studied after bile duct obstruction for 28 days. The biliary secretion of reduced glutathione (GSH), oxidised glutathione (GSSG) and cysteine were completely inhibited in biliary obstructed rats. Hepatic gamma glutamyltranspeptidase (gamma-GT) activity increased significantly, but following its inhibition by acivicin administration GSH, GSSG and cysteine were still absent in bile. Biliary obstruction resulted in a significant increase of the permeability of the paracellular pathway, as shown by the higher bile/plasma ratio and hepatic clearance of [14C]sucrose. GSH and GSSG were, however, significantly lower in the carotid artery and hepatic vein of obstructed animals and the arteriovenous difference across the liver was reduced. The concentration of GSH was significantly reduced and that of GSSG increased in the liver of obstructed rats. Biliary obstruction induced an increase in the hepatic concentration of cysteine and an inhibition of both gamma glutamylcysteine synthetase and methionine adenosyl transferase activities. Dichlorofluorescein (DCF) and the GSSG/GSH ratio and thiobarbituric acid reactive substances (TBARS) concentration, markers of reactive oxygen species production and lipid peroxidation, respectively, were significantly increased. Our data indicate that increased degradation or blood reflux of glutathione do not participate in the disruption of its secretion into bile and support the view that impairment of glutathione synthesis and oxidative stress could contribute to the decline in biliary glutathione output.     

The efficiency of CAPE on retardation of hepatic fibrosis in biliary obstructed rats

The aim of this study was to evaluate the possible protective effects of caffeic acid phenethyl ester (CAPE) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. A total of 18 male Sprague–Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received CAPE; each group contain 6 animals. The rats in CAPE treated groups were given CAPE (10 μmol/kg) once a day intraperitoneally (i.p) for 2 weeks starting just after BDL operation. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with CAPE attenuated alterations in liver histology. The proliferating cell nuclear antigen and the activity of TUNEL in the BDL were observed to be reduced with the QE treatment. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme (superoxide dismutase (SOD), glutathione peroxidase (GPx)) activities. CAPE treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The data indicate that CAPE attenuates BDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of CAPE is associated with antioxidative potential.     

Impact of bile duct obstruction on hepatic E. coli infection: role of IL-10

Biliary obstruction in the setting of hepatic bacterial infection has great morbidity and mortality. We developed a novel murine model to examine the effect of biliary obstruction on the clearance of hepatic Escherichia coli infection. This model may allow us to test the hypothesis that biliary obstruction itself adversely affects clearance of hepatic infections even if the bacteria are introduced into the liver by a nonbiliary route. We ligated the bile ducts of C57BL/6 mice on days -1, 0, or +1, relative to a day 0 portal venous injection of E. coli. We monitored survival, hepatic bacterial growth, pathology, and IL-10 protein levels. The role of IL-10 in this model was further examined using IL-10 knockout mice. Mice with bile duct ligation at day +1 or 0, relative to portal venous infection at day 0, had decreased survival compared with mice with only portal venous infection. The impaired survival was associated with greater hepatic bacterial growth, hepatic necrosis, and increased production of IL-10. Interestingly, the transgenic knockout of IL-10 resulted in impaired survival in mice with bile duct ligation and portal venous infection. Biliary obstruction had a dramatic detrimental effect on hepatic clearance of portal venous E. coli infection. This impaired clearance is associated with increased IL-10 production. However, transgenic knockout of IL-10 increased mortality after hepatic infection.     

一氧化氮在大鼠肝肺综合征发病机制中的作用研究

目的探讨一氧化氮（NO）在大鼠肝肺综合征（HPS）发病机制中的作用。方法应用放射免疫分析法检测HIS大鼠血浆和肝组织、肺组织匀浆中NO的水平。结果（1）HIS大鼠血浆和肝组织、肺组织匀浆中NO水平动态升高。（2）各阶段血浆和肝组织、肺组织匀浆中NO水平与谷丙转氨酶（ALT）、总胆红素（TBIL）呈正相关,出现腹水者血浆和肝组织、肺组织匀浆中NO水平高于未出现腹水者。结论在HIS形成过程中,血浆和肝组织、肺组织匀浆中NO水平持续升高,与肝功能受损状态和腹水形成有关,提示扩血管物质NO可能参与HIS的发生。     

降钙素基因相关肽在大鼠肝肺综合征发病机制中的作用

目的探讨降钙素基因相关肽(CGRP)在大鼠肝肺综合征(HPS)发病机制中的作用。方法应用放射免疫分析法检测HPS大鼠血浆和肝组织、肺组织匀浆中CGRP的水平。结果(1)HPS大鼠血浆和肝组织、肺组织匀浆中CGRP水平动态升高。(2)各阶段血浆和肝组织、肺组织匀浆中CGRP水平与谷丙转氨酶(ALT)、总胆红素(TBIL)呈正相关。结论在HPS形成过程中,血浆和肝组织、肺组织匀浆中CGRP水平持续升高,与肝功能受损状态和腹水形成有关,提示血管活性物质CGRP可能参与HPS的发生。     

异甘草酸镁对胆道梗阻致肝损伤肝功能保护作用的动物实验研究

目的:探讨异甘草酸镁注射液对大鼠梗阻性黄疸肝损伤的保护作用。方法:选用健康雄性SD大鼠32只,随机分成4组,每组各8只,分别为胆总管结扎+异甘草酸镁注射液常规剂量组(BMc组);胆总管结扎+异甘草酸镁注射液高剂量组(BMh组);胆总管结扎+0.9%生理盐水注射液组(BN组)和假手术组(Sham组)。BN和Sham组以生理盐水30 mg/kg/日腹腔注射,BMc组以异甘草酸镁30 mg/kg/日腹腔注射,BMh组以异甘草酸镁60 mg/kg/日腹腔注射。术后不同时间对各组大鼠眼眶取血并获得血清。在全自动生化分析仪器检测肝功能指标:丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、直接胆红素(Direct bilirubin,DBil)。结果:BN、BMc和BMh组大鼠在胆管结扎后血清中ALT和AST指标明显升高。随着梗阻时间的增加,BM和BMh组大鼠血清中ALT和AST的水平均明显低于BN组(P0.01),但两组之间并无明显区别。手术后BN、BMc和BMh组大鼠在胆管结扎后血清中D-Bil水平明显高于Sham组(P0.01),但随着梗阻时间的延长,各组间D-Bil的水平变化不明显。结论:异甘草酸镁注射液可以有效降低梗阻性黄疸大鼠血清转氨酶水平,对肝功能有明显的保护作用。