ABSTRACT
This study aimed to investigate the effect of Tibetan medicine Ershiwuwei Songshi Pills(ESP) on the intestinal flora of non-alcoholic steatohepatitis(NASH) mice. Forty-eight male C57 BL/6 mice were randomly divided into the control group, model(methionine-choline-deficient, MCD) group, high-(0.8 g·kg~(-1)), medium-(0.4 g·kg~(-1)), and low-dose(0.2 g·kg~(-1)) ESP groups, and pioglitazone(PGZ, 10 mg·kg~(-1)) group, with eight mice in each group. Mice in the control group were fed with normal diet, while those in the remaining five groups with MCD diet for five weeks for inducing NASH. During modeling, they were gavaged with the corresponding drugs. The changes in body mass, daily water intake, and daily food intake were recorded. At the end of the experiment, the liver tissues were collected and stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by oil red O staining for observing fat accumulation in the liver. The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and triglyceride(TG) in liver tissue were measured. The changes in intestinal flora of mice were determined using 16 S rRNA high-throughput sequencing technology. The results showed that compared with the model group, the high-, medium-and low-dose ESP groups and the PGZ group exhibited significantly lowered AST and ALT in serum and TG in liver tissues and alleviated hepatocellular steatosis and fat accumulation in the liver. As demonstrated by 16 S rRNA sequencing, the abundance index and diversity of intestinal flora decreased in the model group, while those increased in the ESP groups. Besides, the Firmicutes to Bacteroidetes ratio decreased at the phylum level. In the alteration of the composition of intestinal flora, ESP reduced the abundance of Erysipelotrichia and Faecalibaculum but increased the abundance of Desulfovibrionaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. This study has revealed that ESP has a protective effect against NASH induced by MCD diet, which may be related to its regulation of the changes in intestinal flora, alteration of the composition of intestinal flora, and inhibition of the intestinal dysbiosis.
Subject(s)
Animals , Male , Mice , Disease Models, Animal , Gastrointestinal Microbiome , Liver , Medicine, Tibetan Traditional , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/drug therapyABSTRACT
Objective • To construct a non-alcoholic steatohepatitis (NASH) mouse model by the combination of Western diet (WD) and low-dose carbon tetrachloride (CCl4), and explore the time nodes of typical NASH pathological changes. Methods • Male 8-week C57BL/6 mice were fed WD and intraperitoneally injected with CCl4 at a dose of 2 μL/g of body weight per week to construct NASH models. At different time points, the fasting blood glucose, and the levels of triacylglyceride, glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase were tested; glucose tolerance was tested at the 24th week. Besides, the liver index was calculated and oil red O staining, Sirius red staining, hematoxylin-eosin staining and TUNEL test were conducted to evaluate liver pathological changes after liver sampling. Results • Between the control group and model group, there was no significant difference in fasting blood glucose and glucose tolerance test result, while the significant differences of liver index were observed at the 8th, 12th and 24th week (P<0.05). And at the 24th week, the levels of triacylglyceride, glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase were higher in the model group than those in the control group (P<0.05). According to the results of oil red O staining, Sirius red staining, hematoxylin-eosin staining and TUNEL test, in the model group, a large amount of small lipid droplets accumulation in the liver tissues was detected and hepatocytes were mainly in apoptotic state at the 8th week; large lipid droplets, hepatocellular ballooning and spot-like necrosis were observed, and hepatocyte apoptosis persisted at the 16th week; stage 3 fibrosis of liver was observed, and the number of spot-like necrosis increased but lipid droplets decreased, while hepatocytes were mainly in a proliferative state at the 24th week. Conclusion • The mouse model of NASH can be established successfully by WD combined with low-dose CCl4, which can simulate the pathologic features of NASH in a short time.
ABSTRACT
La obesidad es el factor que más se asocia a la esteatohepatitis no alcohólica (EHNA). La cirugía bariátrica ha demostrado ser eficaz en la EHNA y junto con el tratamiento de la diabetes mellitus tipo 2 (DMT2) y la dislipidemia, logran una mejoría en las alteraciones de las enzimas hepáticas y de los cambios ecográficos hepáticos. Objetivo: Analizar el efecto de la cirugía bariátrica en pacientes con índice de masa corporal (IMC) ≥ 35 kg/m2 y EHNA. Método: se hizo una investigación retrospectiva de 20 pacientes sometidos a cirugía bariátrica: bypass gástrico en Y de Roux (BPGYR) y gastrectomía vertical (GV) entre 2014 y 2015. Resultados: De los 20 pacientes, 14 fueron intervenidas de BPGYR y 6 de GV; 95% fueron del sexo femenino, con edad promedio de 35,95 ± 8,54 años. Los valores preoperatorios de aspartato aminotransferasa (AST) y alanino aminotransferasa (ALT) de todos los pacientes fue > 30 U/L. Los valores postoperatorios de AST y ALT al año de la cirugía fueron normales en 85% y 80% de los casos respectivamente. No se observaron alteraciones en los niveles pre y postoperatorios de lactato deshidrogenasa (LDH). Todos los pacientes presentaron infiltración grasa hepática moderada la cual se redujo a leve o sin infiltración grasa al año de la cirugía de acuerdo a la evaluación ecográfica. Conclusiones: La cirugía bariátrica demostró tener un impacto favorable en EHNA dado por la mejoría en los niveles de AST, ALT y de la esteatosis hepática corroborada por controles ecográficos(AU)
Obesity is the factor that is most associated with non-alcoholic steatohepatitis (NASH). Bariatric surgery has been shown to be effective in NASH and, along with treatment of type 2 diabetes (T2D) and dyslipidemia, they achieve a significant improvement in liver enzymes and liver ultrasound changes. Objective: To analyze the effect of bariatric surgery in patients with a body mass index (BMI) > 35 kg/m2 and NASH. Method: It was performed a retrospective investigation of 20 patients who underwent bariatric surgery: Roux-en-Y gastric bypass (RYGBP) or sleeve gastrectomy (SG) between 2014 and 2015. Results: Of the 20 patients, 14 underwent BPGYR and 6 GV; 95% were female, with a mean age of 35.95 ± 8.54 years. The preoperative levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for all patients were >30 U/L. Postoperative levels of AST and ALT one year after surgery were normal in 85% and 80% of cases, respectively. No alterations were observed in pre and postoperative levels of lactate dehydrogenase (LDH). All patients presented moderate hepatic fat infiltration which was reduced to mild or without fat infiltration one year after surgery according to the ultrasonographic evaluation. Conclusions: Bariatric surgery was shown to have a favorable impact on NASH due to the improvement observed in AST and ALT levels, and hepatic steatosis corroborated by ultrasound scans(AU)
Subject(s)
Humans , Male , Female , Adult , Gastric Bypass , Diabetes Mellitus, Type 2 , Bariatric Surgery , Non-alcoholic Fatty Liver Disease/etiology , Obesity/complications , Body Mass Index , Prevalence , Dyslipidemias , GastrectomyABSTRACT
This study aimed to investigate the molecular mechanism and protective effect of total saponins of Panax japonicas (TSPJ) on HepG2 cells apoptosis induced by palmitic acid (PA).The HepG2 cells were cultured , and divided into five groups: the control group, the model group, the high-dose group (50 mg·L⁻¹), the middle-dose group (25 mg·L⁻¹) and the low-dose group (12.5 mg·L⁻¹).The cells of the five groups were cultured continuously for 24 hours. The cell viability was measured with MTT. HepG2 cells apoptosis was detected by Hoechest staining and Annexin V-FITC/PI staining. The protein expressions of BCL-2, CHOP and TLR4 were measured with western blotting and flow cytometry analysis. The mRNA expressions of TNF-α, IL-1β, BCL-2, CHOP and GAPDH were measured with RT-PCR. The results suggested that compared with the control group, the number of HepG2 cells of the model group were reduced significantly (<0.01), while the number of apoptotic HepG2 cells were increased. Compared with the model group, the number of HepG2 cells of the high-dose group and the middle-dose group were increased significantly (<0.01), whereas the number of apoptotic HepG2 cells were reduced. Compared with the control group, TNF-α, IL-1β and CHOP mRNA expressions and CHOP and TLR4 protein expressions in the model group were significantly up-regulated (<0.01), while BCL-2 protein and mRNA expressions in the model group were significantly decreased (<0.01). Compared with the model group, TNF-α, IL-1β and CHOP mRNA expressions and CHOP and TLR4 protein expressions in the high-dose group were significantly decreased (<0.01), while BCL-2 protein and mRNA expressions in the high-dose group were significantly up-regulated (<0.01).In conclusion, TSPJ can reduce inflammation and apoptosis induced by palmitic acid, with a certain protective effect on liver cells.
Subject(s)
Humans , Apoptosis , Hep G2 Cells , Palmitic Acids , Panax , Chemistry , Phytochemicals , Pharmacology , Saponins , PharmacologyABSTRACT
AIM To observe the clinical efficacy of Huazhi Rougan Granules (Artemisiae scopariae Herba,Cassiae Semen,Rhei Radix et Rhizoma,etc.) in the treatment of damp-heat accumulation type non-alcoholic steatohepatitis (NASH) and its influence on insulin resistance.METHODS During January 2014-January 2016,a total of one hundred and twenty patients with damp-heat accumulation type NASH,given diet and exercise guidance,were randomly and equally divided into control group (polyene phosphatidylcholine) and treatment group (Huazhi Rougan Granules),administrated for twelve weeks.The levels of serum alanine aminotransferase (ALT),aspartate aminotranferase (AST),gamma-glutamyltransferase (GGT),total cholesterol (TC),triglyceride (TG),γ-glutamyl transpeptadase (GGT),fasting plasma glucose (FPG),fasting insulin (FINS),HOMA-IR index,adiponectin (ADPN) and leptin,body mass index (BMI) and uhrasound examination were detected before and after the treatment,respectively.These data were compared in two groups.RESULTS Compared with the control group,the serum ALT,AST,GGT,TC,TG,FPG,FINS and HOMA-IR of the patients in the treatment group decreased significantly,and liver fat were effectively reduced,while serum adiponectin increased markedly (P ＜ 0.05).After the treatment,remarkable reductions in the levels of BMI,leptin were observed in both groups (P ＜ 0.05).CONCLUSION Huazhi Rougan Granules combined with lifestyle modulation can effectively improve the syndrome of damp-heat accumulation type NASH by lowing insulin resistance.
ABSTRACT
Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest in PUFA derived from their potential benefit in cardio-metabolic disease and the close association of NAFLD/NASH with Metabolic Syndrome. Results have been variable although most studies show reduction of liver fat without other major effects and their effects are influenced by concomitant weight loss and underlying genetic factors. Vitamin E has had some efficacy in pediatric NASH but questionable efficacy in even mild NASH among adults. Pioglitazone has shown significant histological benefit in a number of trials but concern over side-effects (especially weight gain) have dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown promise in a small randomized, controlled trial. Very limited data exists regarding the histological effects of the statins in NASH and these agents appear to be fairly neutral with neither clear cut benefit nor detriment. Their use is best guided by cardiovascular risks rather than liver histology.
Subject(s)
Adult , Humans , Fatty Liver , Fibrosis , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypertension, Portal , Insulin , Liraglutide , Liver , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Vitamin E , Vitamins , Weight LossABSTRACT
Introducción: la cirrosis es la condición médica final de diversas enfermedades hepáticas de carácter progresivo, con una prevalencia variable de un país a otro; en la actualidad, el abuso de alcohol, el hígado graso no alcohólico y las hepatitis crónicas virales son mencionados como sus principales causas. En nuestros centros no se dispone de estudios clínicos en relación con esta enfermedad. Materiales y métodos: estudio retrospectivo y descriptivo de pacientes con diagnóstico de cirrosis hepática entre el 1 de enero del 2010 al 31 de marzo del 2014. Se realizó revisión de historias clínicas. Resultados: la serie incluyó 419 pacientes, 50,1% mujeres y 49,9% hombres, con una edad promedio de diagnóstico de cirrosis de 63 años; el 73% de los pacientes presentaban hallazgos de hepatopatía crónica en el examen físico y el 27% tenía un examen físico normal. Las principales etiologías en esta serie fueron: esteatohepatitis no alcohólica (25,5%), alcohólica (14,8%), infección por virus C (14,6%), autoinmunidad (10%), esteatohepatitis no alcohólica más alcohol (6,7%), y otras (14,6%). La clasificación de Child-Pugh se pudo calcular en 394 pacientes y de estos, el 59,1%, 32,4% y 8,3% eran A, B y C, respectivamente. En relación con las descompensaciones, las principales fueron ascitis (36,1%), sangrado variceal (28,4%) y hepatocarcinoma (15,3%). Conclusiones: el comportamiento epidemiológico local no difiere en relación con el mundial. Llama la atención su detección en fases tempranas y la NASH como factor etiológico principal.
Introduction: Cirrhosis is the final medical condition of various progressive liver disease. Its prevalence varies from one country to another. Currently alcohol abuse, non-alcoholic fatty liver disease and chronic viral hepatitis are mentioned as the main causes. In our centers we have no clinical studies regarding this disease. Materials and Methods: This is a retrospective, descriptive study of the clinical histories of patients who were diagnosed with liver cirrhosis between January 1, 2010 to March 31, 2014. Results: The study included 419 patients, 50.1% of whom were women and 49.9% of whom were men. The average age at diagnosis of cirrhosis 63 years. 73% of patients had physical findings of chronic liver disease and 27% had normal physical examinations. The main etiologies in this series were nonalcoholic steatohepatitis (25.5%), alcoholic cirrhosis (14.8%), hepatitis C infection (14.6%), autoimmune cirrhosis (10%), nonalcoholic steatohepatitis plus alcohol (6.7%), and others (14.6%). The Child-Pugh classification could be calculated in 394 patients. Of these 59.1% were classified A, 32.4% were classified B, and 8.3% were classified C. The primary reasons for decompensation ascites (36.1%), bleeding varices (28.4%) and hepatocellular carcinoma (15.3%). Conclusions: Local epidemiological behavior does not differ from those found elsewhere in the world. Attention needs to be paid to detection in early stages and NASH as the main etiological factor.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Ascites , Gastroenterology , Liver Cirrhosis , Non-alcoholic Fatty Liver DiseaseABSTRACT
Introduction: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumour, which commonly occurs in those with underlying chronic liver problems mainly cirrhoric liver with viral hepatitis (HBV and HCV) as the most common aetiological agent. HCC could also arise from non-chronic liver, which include non-B non-C (NBNC) hepatitis, which is different in pathogenesis, epidemiology and prognosis. This disease entity would include the commonly benign fatty liver leading to non-alcoholic steatohepatitis (NASH) and HCC as sequale. Methods: We present a case of non-B non-C HCC arising from a fatty liver in a non-alcoholic patient. Literature search was done with special emphasis on this disease. Conclusion: The incidence of NBNC HCC demonstrates an increasing trend, making it an important entity to be recognised early. A good understanding of this incidence would make it possible to predict the outcome, especially as the prognosis of non-B non-C HCC is fairly good if the HCC is found at an early stage