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ObjectiveBased on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway， this paper explores the effect of Sinisan （SNS） on liver oxidative stress injury in cholestatic hepatitis rats and its mechanism. MethodThirty 6-week-old male SD rats were randomly divided into a control group， model group， low and high dose groups of SNS （2.5 and 5 g·kg-1） and ursodeoxycholic acid group （UDCA， 63 mg·kg-1）， with six rats in each group. Rats were administrated for seven consecutive days. On the 5th day， the control group was given olive oil of 10 mL·kg-1， and the other groups were given alpha-naphthalene isothiocyanate （ANIT） of 80 mg·kg-1. The serum biochemical indicator levels of cholestasis and the content of antioxidant factors in rat liver were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in liver tissue. The relative mRNA and protein expressions of Nrf2， HO-1， and quinone oxidoreductase 1 （NQO1） in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the model group showed a significant increase in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）. There were obvious pathological changes in the model group such as the disordered arrangement of hepatocytes， obvious congestion and necrosis in the portal area， infiltration of inflammatory cells， and destruction of the interlobular bile duct. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly down-regulated in the model group （P<0.05， P<0.01）. Compared with the model group， the groups of SNS showed a significant decrease in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）， and the pathological liver injury was obviously improved. The necrotic area was reduced， and the infiltration of inflammatory cells was decreased. In addition， there was a small amount of extravasated blood in the interlobular vein. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly up-regulated （P<0.05， P<0.01）. ConclusionSNS can significantly improve liver injury in cholestatic hepatitis rats， and its mechanism may be related to the inhibition of oxidative stress response mediated by the Nrf2/HO-1 signaling pathway.
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La ictericia colestásica se debe a la alteración de la secreción de bilirrubina conjugada; es una de las posibles causas la alteración del flujo biliar por obstrucción de la vía biliar extrahepática. El linfoma es la tercera neoplasia más frecuente en pediatría, mientras que los tumores pancreáticos son poco frecuentes y, en su mayoría, lesiones benignas. Las manifestaciones clínicas de los tumores de localización retroperitoneal son poco específicas y suelen ser tardías, por lo que la sospecha clínica debe ser alta. El objetivo del siguiente trabajo es presentar el caso de un niño de 7 años con síndrome colestásico en el que se halló un tumor en la cabeza del páncreas que comprimía la vía biliar extrahepática. El diagnóstico del tumor fue linfoma no Hodgkin (LNH). Se destaca la infrecuencia de este tumor en esta localización en la edad pediátrica
Cholestatic jaundice is due to an alteration in conjugated bilirubin secretion; a possible cause is an altered bile flow resulting from an obstruction of the extrahepatic bile duct. A lymphoma is the third most common neoplasm in pediatrics, while pancreatic tumors are rare and mostly benign. The clinical manifestations of retroperitoneal tumors are not very specific and are usually late, so a high level of clinical suspicion is required. The objective of this study is to describe the case of a 7-year-old boy with cholestatic syndrome with a tumor in the head of the pancreas compressing the extrahepatic bile duct. The tumor diagnosis was non-Hodgkin lymphoma (NHL). It is worth noting that the presence of a tumor in this location in pediatric age is uncommon
Subject(s)
Humans , Male , Child , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/pathology , Cholestasis/etiology , Jaundice, Obstructive/diagnosis , Jaundice, Obstructive/etiology , Jaundice, Obstructive/pathology , Pancreas , Syndrome , Cholestasis/diagnosisABSTRACT
OBJECTIVE To study the effects of Hugan buzure formula （HBF） on intrahepatic cholestatic liver injury in rats and its potential mechanism. METHODS Rats were randomly divided into control group， model group， ursodeoxycholic acid （UDCA） group （positive control， 60 mg/kg ） and HBF low-dose， middle-dose and high-dose groups （HBF-L， HBF-M， HBF-H groups， 0.4， 0.8， 1.6 g/kg ）， with 6 rats in each group. The rats in each drug group were given the corresponding drug solution intragastrically， once a day， for 7 consecutive days. The rats in the control group and the model group were given equal volumes of water intragastrically. On the 5th day， except for the control group， the rats in other groups were single intragastrically administered with alpha-naphthyl isothiocyanate olive oil solution （100 mg/kg） to establish the model. After 48 h of modeling， the contents of liver function indexes （aspartate aminotransferase， alanine aminotransferase， alkaline phosphatase， total bile acid， total bilirubin， direct bilirubin） and oxidative stress indexes [malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase] in serum of rats were detected； the pathological changes of liver tissue were observed. The mRNA expressions of inflammation-related factors [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）] and farnesoid X receptor （FXR） signaling pathway-related factors [FXR， small heterodimer partner （SHP）， multidrug resistance protein 2 （MRP2）， bile salt export pump （BSEP）， Na+-taurocholate cotransporting polypeptide （NTCP）， organic anion-transporting polypeptide 2 （OATP2） and cholesterol 7α-hydroxylase （CYP7A1）]， the expressions of FXR signaling pathway-related proteins （FXR， MRP2， BSEP， NTCP） and nuclear factor- κB p65 （NF- κB p65） in liver tissue were detected.RESULTS Compared with the model group， the contents of liver function indexes and the level of MDA in serum， the mRNA expressions of the above inflammation-related factors and CYP7A1， and the relative expression of NF-κB p65 in liver tissue were significantly decreased； the levels of GSH in serum， the mRNA expressions of FXR， SHP， MRP2， BSEP， NTCP and OATP2， and the relative expressions of FXR， MRP2， BSEP and NTCP in liver tissue were significantly increased （P＜0.05 or P＜0.01）； the pathological changes of liver tissue were significantly improved. Only some indexes in HBF-L group， HBF-M group and UDCA group were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS HBF can prevent intrahepatic cholestatic liver injury in rats， and the effects may be related to the activation of FXR signaling pathway and the reduction of inflammation and oxidative stress.
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Cholestatic jaundice is rare in patients with Graves' disease and is generally considered to be a complication of Graves' disease or an adverse reaction to methimazole. We report a case of acute cholestatic jaundice caused by Graves' disease complicated with upper respiratory tract infection in Jinan Central Hospital. After timely treatment with glucocorticoid, the jaundice quickly subsided and the liver function gradually returned to normal. We believe that Graves' disease combined with upper respiratory tract infection can lead to cholestatic jaundice, the pathogenesis of which may be immune dysfunction, and glucocorticoid therapy is beneficial to the regression of jaundice.
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Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.
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Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.
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Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CXAE, CXAL, CXPA and CXPHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-β (TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CXAE, CXAL and CXPHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CXAE and CXPHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β. CXPHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CXPHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CXPHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.
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Drug induced liver injury (DILI) has been a long-standing concern in the treatment of tuberculosis. Anti-tuberculosis therapy (ATT) is known to have hepatotoxicity effect. DILI is diagnosed clinically using liver biochemical test, such as alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin. Calculating ratio (R) of ALT over ALP, is useful to classify types of injury pattern in DILI. Roussel Uclaf causality assessment method (RUCAM)scaleserves as a method to assess the causality agents for DILI. Here we report a case of 59 years old male who developed cholestatic DILI on fourth weeks of ATT. Patient came in with loss of consciousness, jaundice, nausea, pruritus, and abdominal tenderness. Patient抯 ALT level was normal, but ALP and total bilirubin was significantly elevated, with R values less than 2, indicating a cholestatic type of injury. Patient sputum was positive for tuberculosis bacteria, showing an active infection. Patient was admitted and ATT was discontinued. Patient showed improvement, but eventually fall into sepsis and developed respiratory distress on sixth day of admission despite adequate treatment and close monitoring. Despite most of the cases resolves spontaneously upon cessation of the toxic agents, in the severe form, it may fall into chronic liver injury, acute liver failure, and eventually death. Preventing DILI is readily important by educating, screening for risk factors, and routine evaluation of liver enzymes in patient under ATT. Early diagnosis and prompt treatment are needed to avoid poor prognosis in the course of the disease.
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Objective:To investigate the clinical and genetic characteristics of genetic and metabolic infantile cholestatic hepatopathy (ICH), and to provide evidence for its diagnosis and treatment.Methods:Clinical data and follow-up outcomes of hospitalized children diagnosed with ICH in the Department of Gastroenterology, Children′s Hospital, Capital Institute of Pediatrics from January 2014 to December 2019 were retrospectively analyzed.Among the 80 children, 27 were female and 53 were male, with a mean age of onset of (39±18) days old.Children with confirmed etiology by high-throughput sequencing analysis were included in the genetic metabolic group (44 cases), and those with idiopathic neonatal cholestasis(INC) of unknown etiology after the systematic examination were included in the INC group (36 cases). The t-test or independent sample rank sum test was used to compare the laboratory test results and biochemical indexes.The infection rate of cytomegalovirus was compared by the Chi- square test. Results:(1) A total of 80 cases were included, and 44 cases (55.0%)were confirmed as INC by high-throughput sequencing.Among those with a positive molecular diagnosis, there were 23 cases of citrin deficiency (CD), 10 cases of Alagille syndrome (ALGS), 6 cases of progressive familial intrahepatic cholestasis (PFIC), 2 cases of congenital bile acid synthesis defect, 2 cases of Nieman Pick disease, and 1 case of cystic fibrosis.(2) Serum total bile acid (TBA) and activated partial prothrombin time (APTT) levels in the genetic metabolic group were significantly higher than those in the INC group (all P<0.05). TBA and APTT levels in genetic metabolites were 180.6 (115.5, 271.6) μmol/L and 40.6 (37.1, 45.2) s, respectively, which were 123.3 (98.8, 163.4) μmol/L and 34.8 (31.7, 40.1) s in INC group, respectively.There was no significant difference in the cytomegalovirus infection rate between the 2 groups ( P>0.05). (3)The pathological examination of liver tissue in the genetic metabolic group was worse than that in the INC group, with spot-like and fusion focal-like necrosis, and 5 cases (4 cases of ALGS and 1 case of CD) showed a reduced number of bile ducts in the portal area and lumen stenosis. Conclusions:CD, ALGS and PFIC are the common causes of genetic and metabolic ICH.Fundamental cause of cholestasis should be actively examined in children with cytomegalovirus infection.High-throughput sequencing is of great significance in the accurate diagnosis of ICH.
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El neurofibroma de la vía biliar es una enfermedad extremadamente rara y generalmente asintomática, sin embargo, puede ocasionar ictericia obstructiva y simular un tumor de Klatskin conduciendo a un tratamiento quirúrgico radical y mayor morbilidad del paciente. Presentamos el caso de una mujer de 62 años colecistectomizada hace 10 años, con ictericia y dolor en hipocondrio derecho, así como exámenes auxiliares compatibles con colestasis. Se observó dilatación de la vía biliar y presencia de un tumor en el conducto hepático izquierdo mediante colangioresonancia magnética. El diagnóstico clínico preoperatorio fue Colangiocarcinoma hiliar, pero el estudio histopatológico reveló una neoplasia compuesta por células fusocelulares sin atipia ni actividad mitótica, cuya estirpe neurogénica se sustentó por su positividad a proteína S100 en inmunohistoquímica. Reportamos el caso dada su poca frecuencia en la literatura y su relevancia, al ser una entidad benigna, como diagnóstico diferencial de cáncer.
The neurofibroma of the bile duct is an extremely rare and generally asymptomatic disease, however, it maybe cause obstructive jaundice and mimic a Klatskin tumor, leading to radical surgical treatment and increased patient morbidity. We present the case of a 62-year-old woman who underwent cholecystectomy 10 years ago, with jaundice and pain in the right upper quadrant, as well as auxiliary tests compatible with cholestasis. Dilation of the bile duct and the presence of a tumor in the left hepatic duct were observed by magnetic cholangioresonance. The preoperative clinical diagnosis was hilar cholangiocarcinoma, but the histopathological study revealed a neoplasm composed of spindle cells without atypia or mitotic activity, whose neurogenic lineage supported by its positivity to protein S100 in immunohistochemistry. We report the case given its infrequency in the literature and its relevance, as it is a benign entity, as a differential diagnosis of cancer.
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Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 μg·kg
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Cholestatic hepatopathy is a hepatobiliary system disease caused by abnormal bile excretion.It is common in infants.And its incidence varies with region and cause.The incidence of cholestatic jaundice in full-term infants is about 1/2 500.The etiology of infantile cholestatic hepatopathy involves many factors including abnormal liver or bile ducts structure, genetic metabolic diseases, infections, endocrine diseases and parenteral nutrition-associated cholestasis.The disease needs to be treated according to the primary disease.If there is a clear etiology, etiological treatment is necessary.Usually symptomatic and comprehensive treatment is adopted due to inconclusive diagnosis.The artical mainly states the present therapy methods.
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Objective:To investigate characteristics of fever and drug-induced liver injury (DILI) in inpatients with severe drug eruptions.Methods:A retrospective analysis was carried out on clinical data collected from 63 inpatients with severe drug eruptions from June 2007 to June 2020, and their characteristics of fever and DILI were investigated. Two-independent-sample t test or Kruskal-Wallis H test was used for intergroup comparison of measurement data, and intergroup comparison of enumeration data was performed using chi-square test or Fisher′s exact test. Results:Among the 63 patients with severe drug eruptions, 54 developed fever; low, moderate and high/ultra-high fever all occurred in about one third of the patients; of 17 patients with high/ultra-high fever, 16 sufferred from Stevens-Johnson syndrome (SJS) , toxic epidermal necrolysis (TEN) or drug hypersensitivity syndrome (DHS) ; 45 had irregular fever; fever duration ranged from 1 to 14 days in 51 patients; there were no significant differences in the fever grade or duration among the patients with different clinical types of drug eruptions ( P = 0.303, 0.719, respectively) ; rashes occurred earlier than or at the same time as fever in 92.59% of the patients. DILI occurred in 11 patients, 8 of whom had hepatocellular injury at admission, including 5 with DHS, 2 with SJS and 1 with TEN; 6 patients were accompanied by low, moderate or high fever, with the fever duration being 7.33 ± 4.97 days, and they all had grade 1 liver injury; liver function retesting at discharge showed complete recovery in 5 patients, improvement in 1, as well as conversion from hepatocellular injury to mixed liver injury in 1, and 1 patient did not undergo the liver function retesting due to against-medical-advice discharge. The other 3 patients had cholestatic liver injury, all of whom were diagnosed with DHS and accompanied by high or ultra-high fever, wtih the fever duration being 8.33 ± 3.51 days, and 1 patient had grade 4 liver injury (acute liver failure) ; liver function was improved in all the 3 patients at discharge. Conclusions:Patients with severe drug eruptions are prone to be accompanied by various types of fever, irregular fever is more common, fever usually lasts 2 weeks, and rashes often occur earlier than or at the same time as fever. DILI can occur in patients with severe drug eruptions, and is usually accompanied by fever; hepatocellular injury is more common, and prone to be improved rapidly; cholestatic liver injury is characterized by severe clinical symptoms and a long disease course, and most frequently occurs in patients with DHS.
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Symptomatic acute Epstein-Barr virus (EBV) hepatitis, without associated infectious mononucleosis syndrome, is exceptionally rare. A 30-year-old female presented to hospital with jaundice, fevers, and right upper quadrant abdominal pain. Her blood tests demonstrated marked hyperbilirubinemia and mild global liver function test abnormalities consistent with obstructive jaundice. Preliminary imaging with ultrasound showed gallbladder wall thickening and cholelithiasis, suggestive of potential cholecystitis. Authors were concerned for potential ascending cholangitis in the setting of her hyperbilirubinemia. The diagnosis was refuted after magnetic resonance cholangiopancreatography demonstrated no choledocholithiasis. A hepatic panel was performed which revealed positive EBV IgM serology. This case highlights the importance of considering EBV hepatitis as a potential differential diagnosis in patients with right upper quadrant pain, fevers and jaundice in the absence of an obstructing cause.
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Benign Recurrent Intrahepatic Cholestasis (BRIC) is a rare autosomal recessive disorder characterized by intermittent episodes of jaundice and pruritus. It is also known as Summerskill-Walshe-Tygstrup syndrome. It is a benign disease with no progression to end stage liver disease.. The first episode of cholestatic jaundice occurs early in life and there are asymptomatic periods between attacks lasting weeks to years. This case report presents a young male who presented with severe pruritus and acute onset jaundice. He had his first episode of jaundice at the age of twelve and had several intermittent episodes since then. Diagnosis was made by the unique clinical presentation with exclusion of other causes of cholestatic jaundice. This case report highlights the importance of detecting such cases of rarity and preventing unnecessary invasive diagnostic procedures on such patients.
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Objective::To investigate the protective effect of modified Yinchenhao Tang on α-isothiocyanate(ANIT)-induced cholestatic liver disease (CSLD). Method::Wistar rats were randomly divided into 7 groups: blank control group, model control group, compound Glycyrrhizin capsules group(22.5, 45 mg·kg-1), modified Yinchenhao Tang low, middle and high dose groups(4.1, 8.1, 16.2 g·kg-1). A model of cholestatic liver injury was prepared by intragastric administration of ANIT (100 mg·kg-1). Glycyrrhizin capsules and modified Yinchenhao Tang were administered intragastrically on the second day of modeling for 4 consecutive days. And bile duct intubation was performed on the fifth day to measure the bile flow rate of the rats, and serum was taken to test the total bilirubin(TBIL), direct bilirubin(DBIL), indirect bilirubin(IBIL), alanine aminotransferase(ALT) and total bile acid(TBA) serological indicators of each group. Pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The expression levels of G protein-coupled bile acid receptor(TGR5), nucleotide binding oligomerization domain-like receptor 3(NLRP3) and cysteinyl aspartate specific proteinase-1(Caspase-1) proteins in the iver tissues were detected by Western blot. Result::Compared with the blank control group, bile flow rate in the model group decreased significantly(P<0.01). TBIL, DBIL, IBIL, ALT and TBA level in serum were significantly increased(P<0.01), liver tissue lesions were severe, and significantly increased the expression of liver tissue TGR5 and Caspase-1.Compare with model group, the compound Glycyrrhizin capsules group had no significant effect on bile flow rate and TBIL, DBIL, IBIL, ALT and TBA level in serum. Bile flow rate increased and TBIL, DBIL, IBIL, ALT and TBA level in serum decreased significantly in modified Yinchenhao Tang high dose group. The compound Glycyrrhizin capsules group and modified Yinchenhao Tang group have different extents of improvement the pathological changes of the lung tissues, and the protein expression of TGR5 and Caspase-1 were significantly decreased in the liver tissue(P<0.01). Conclusion::Modified Yinchenhao Tang can effectively treat CSLD in rats, and its mechanism may be related to bile acid and bile acid receptor TGR5-mediated inflammatory factors.
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Cholestatic liver diseases (CLD) are a series of hepatobiliary diseases characterized by dysfunction of bile formation, secretion and excretion and are induced by immune, genetic and environmental factors. The development and pathogenesis of CLD is still unclear, and it has a risk of progression to liver fibrosis and cirrhosis. Traditional medicines such as ursodeoxycholic acid (UDCA), glucocorticoids and immunosuppressants have certain limitations. More and more studies provide new insights into the mechanism of cholestasis to explore the therapeutic targets, and various drugs such as all-trans retinoic acid, microecologics and norursodeoxycholic acid emerge as new therapeutic drugs. This article reviewed the advances in treatment of CLD.
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Objective: To investigate the effects of hepatic stem cells survival in the pathological microenvironment of cholestatic cirrhosis, and the effects of sodium glycosaminodeoxycholate (GCDC) on apoptosis of hepatic stem cells in vitro. Methods: Balb/c mice were subjected to bile duct ligation (BDL) to simulate the pathological environment of cholestatic cirrhosis; Liver stem cells HP 14-19 were transplanted back into liver by the splenic vein and survival of cell colonization was detected; Effects of sodium glycosaminodeoxycholate on the viability of HP 14-19 cells at different concentrations by cell counting kit-8(CCK-8) and crystal violet staining, flow cytometry was used to detect the apoptosis of HP14-19 cells treated with 600 μmol/L GCDC 24 hours later, and the expression of Bax, Bcl-2, Capase-3, phosphorylated adenosine 5′-monophosphate-activated protein kinase α (p-AMPKα) and adenosine 5′-monophosphate-activated protein kinase α (AMPKα) were detected by Western blotting. Results: The results of CCK-8 and crystal violet staining showed that the proliferation of HP 14-19 cells was inhibited with the increase of the concentration of sodium glycosaminodeoxycholate. Flow cytometry showed that the apoptosis rate of GCDC treated group was higher than that of control group. Compared with the control group, the expression of Bax, Capase-3 was up-regulated and the expression of Bcl-2 protein was down-regulated in the experimental group. The results showed that GCDC could induce apoptosis of HP14-19 (P<0.05) AMPK was activated. Conclusion: Microenvironment of cholestatic cirrhosis induced apoptosis of liver stem cells.
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@#The occurrence of cholestatic liver injury is accompanied by the alterations of hepatocyte polarization and bile acid homeostasis. Located in epithelial cells, tight junctions(TJs)are a special barrier structure which are important in maintaining permeability and bile acid homeostasis. Based on the fully analysis and discussion of TJs, the latest therapeutic drugs for cholestasis were summaried, which may provide new perspectives and potential therapeutic agents for the treatment of cholestatic liver injury.
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OBJECTIVE: To detect the level of fecal primary and secondary bile acids in infants with infantile cholestatic hepatopathy(ICH)and analyze its clinical value. METHODS: Thirty infants with ICH were enrolled in this study,who were diagnosed with infantile cholestatic hepatopathy. Thirty infants with good health condition were enrolled as the healthy control group. The fecal samples were collected respectively in the preparatory treatment phase and treatment phase from infants with ICH and from the healthy infants. Bile acids were extracted from infants' feces and were quantitatively analyzed by liquid chromatography-mass spectroscopy. RESULTS: Among the fecal primary bile acids,the level of cholic acid,chenodeoxycholic and glycochenodeoxycholic acid both in the ICH preparatory treatment group and ICH treatment group was significantly lower than that in the healthy control group(P<0.016).The level of fecal cholic acid and chenodeoxycholic acid of ICH treatment group was higher than in the ICH preparatory treatment group(P<0.016).Among the fecal secondary bile acids,the level of lithocholic acid both in the ICH preparatory treatment group and ICH treatment group was significantly lower than that in the healthy control group(P<0.016),and the level of ursodeoxycholic acid in the ICH preparatory treatment group was lower than that in the ICH treatment group and healthy control group(P<0.016). CONCLUSION: In infants with ICH, the changes of fecal primary bile acids and fecal secondary bile acids have their own characteristics at the early stage of treatment, which may be caused by the short-term treatment,the prognosis of the disease itself and the changes of intestinal function, including intestinal bacteria. Clinical attention should be paid to these changes.