ABSTRACT
ObjectiveTo investigate the effect of Gegen Qinliantang （GGQLT）-medicated serum on free fatty acid （FFA）-induced nonalcoholic steatohepatitis （NASH） in vitro model of human hepatoma cells HepG2. MethodNASH model of HepG2 cells was established in vitro， and the cells were intervened with different volume fractions of GGQLT-medicated serum and resveratrol. Intracellular lipid deposition in each group was detected by oil red O staining， the level of reactive oxygen species （ROS） in each group were detected by flow cytometry， the levels of glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， triglyceride （TG） and malondialdehyde （MDA） in each group were detected by kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of nuclear transcription factor （NF）E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， quinone oxidoreductase 1 （NQO1）， Kelch-like epichlorohydrin-associated protein-1 （Keap1）， NF-κB， thioredoxin interacting protein （TXNIP）， interleukin-1β （IL-1β） in HepG2 cells of each group. The protein expression of Nrf2， TXNIP in cells of each group was detected by Western blot. ResultFFA induced large accumulation of intracellular lipids. Compared with the normal group， the activities of GSH-Px and SOD were significantly decreased （P<0.01） and the contents of TG， ROS and MDA were significantly increased （P<0.05， P<0.01） in the model group. Compared with the model group， all GGQLT groups and resveratrol group could elevate intracellular SOD activity to different degrees （P<0.05， P<0.01） and significantly reduce the levels of intracellular ROS and MDA （P<0.05， P<0.01）， GGQLD high- and medium-dose groups and resveratrol group significantly elevated GSH-Px activity （P<0.01）， GGQLD medium- and low-dose groups and resveratrol group significantly decreased TG content （P<0.05， P<0.01）. Compared with the model group， GGQLT high- and medium-dose groups and resveratrol group could significantly upregulate the mRNA expression levels of Nrf2， HO-1 and NQO1 （P<0.01）， all GGQLT groups and resveratrol group could significantly downregulate the TXNIP protein expression level， as well as significantly downregulate the mRNA expression levels of Keap1， NF-κB （P<0.05， P<0.01）. Nrf2-siRNA transfection of cells revealed that Nrf2 expression was significantly downregulated （P<0.01） in the Nrf2-siRNA group of cells by comparing with NC-siRNA group at the corresponding dose of drugs， and the inhibitory effects of GGQLT and resveratrol on TXNIP， IL-1β were attenuated. ConclusionFFA induces the production of ROS and inflammatory factors in HepG2 cells， and GGQLT can improve the anti-inflammatory and antioxidant capacities of cells， and its mechanism may be related to the regulation of Nrf2/TXNIP signaling pathway， so as to improve NASH.
ABSTRACT
Liver transplantation is the most effective means to treat the related end-stage liver disease caused by non-alcoholic fatty liver disease (NAFLD). But the recurrence rate of NAFLD after liver transplantation is very high due to the affection of obesity, metabolic syndrome and other adverse factors. In recent years, liver transplantation for NAFLD related end-stage liver disease has made some progress both in China and abroad. This article reviews the research progress of NAFLD and liver transplantation for NAFLD.
ABSTRACT
OBJECTIVE@#To explore the mechanism of catgut embedding at back- points on nonalcoholic steatohepatitis (NASH) in rats based on IKK/IKB/NF-κB signaling pathway and downstream inflammatory factors.@*METHODS@#Eighty SPF SD rats were selected, among them 10 rats were selected divided into a normal group (group A), and the remaining 70 rats were fed with high-fat diet to establish NASH model. At the end of 12 weeks, 10 rats were randomly selected to verify whether the model establishment was successful. Then the remaining 60 rats were randomly divided into a model group (group B), a catgut embedding at back- points group (group C), a catgut embedding at abdominal points group (group D), an acupuncture at back- points group (group E), a sham catgut embedding group (group F) and a western medication group (group G), 10 rats in each group. The rats in the group C were treated with catgut embedding at "Ganshu" (BL 18), "Pishu" (BL 20), "Weishu" (BL 21) and "Shenshu" (BL 23); the rats in the group D were treated with catgut embedding at "Daheng" (SP 15), "Fujie" (SP 14), "Huaroumen" (ST 24) and "Tianshu" (ST 25); the rats in the group E were treated with acupuncture at the same acupoints as the group C; the rats in the group F were treated with catgut embedding at back- points but the needle did not enter subcutaneous tissue gamma; the rats in the group G were treated with intragastric administration of vitamin E capsule. All the treatment was given for 4 weeks. The rats in the group A were fed with normal diet until the end of 16 weeks without any intervention. The rats in the group B continued to be fed with high-fat diet until the end of 16 weeks. After the intervention, the liver index was calculated; the liver histomorphology was observed by HE staining; the liver function [alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GGT), alkaline phosphatase (ALP)] and blood lipid [serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL)] were measured by serum biochemistry. The serum levels of TNF-α, IL-6 and IL-1βwere detected by ELISA, and the expressions of IKK-α, NF-κBp65, IL-6, IL-1β and TNF-α proteins in liver tissue were detected by Western blot. The temperature of the conception vessel and the governor vessel was measured by infrared thermography.@*RESULTS@#Compared with the group A, the obvious steatosis and inflammatory cell infiltration were observed in the group B, and the body weight, liver wet-weight and liver index were all increased (0.05), while the temperature of the governor vessel in the group C was superior to that in the group D (<0.05).@*CONCLUSION@#The catgut embedding at back- points might inhibit the activation of IKK/IKB/NF-κB signaling pathway to interrupt the inflammatory cascade, and reduce the "second hit" of inflammatory factors on liver, which could slow down NASH progress and prevent and treat NASH.
Subject(s)
Animals , Rats , Acupuncture Points , Catgut , NF-kappa B , Non-alcoholic Fatty Liver Disease , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Liver detoxifies the various metabolic products inside thebody and converts toxic substance to less toxic by differentphases of detoxification reaction. It play broad-spectrumrole (synthetic, storage, metabolic, protective secretary andExcretory). Sedentary life style, Unhygienic food, adulteratedfood, high dose of alcohol, fatty diet adversely affect the normalfunctioning of liver. Fatty Liver Disease refers to a reversiblecondition in which there is accumulation of triglyceride fatinto intra-cytoplasmic Vacuole. If fatty liver is not treatable attime then it goes to various stages (NAFLD, NASH, Fibrosis,Cirrhosis and Hepatocellular Carcinoma). Diet and aerobicexercise plays an important role in management of Liverdisease. The present article focused on fatty liver disease ismanageable at earlier stage by spreading awareness programamong the individual.
ABSTRACT
Objective To observe the change of intestinal microflora on the process of nonalcoholic steatohepatitis(NASH),and to explore the synbiotics therapeutic effect on NASH.Methods Rats were administrated with high fat diet to establish NASH model.In the process of NASH rats modeling,the level of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low density lipoprotein (LDL), fasting blood sugar (FBS) and fasting insulin (FINS) was dynamically tested by automatic biochemical analyzer.The change of main intestinal flora was detected by 16 S rRNA fluorescence quantitative polymerase chain reaction.NAFLD activity score was calculated.HE staining was used to observe the hepaticpathological changes and the TLR4 expression was detected by using enzyme-linked immunosorbent assay and immunohistochemical method.Until the 4th,8th,10th weekin the process of NASH modeling, 10 rats were feeded with synbiotics for 2 weeks, and all of above indicators were tested and observed.Results 1)With the extension of a high-fat diet feeding time, the degree of hepatocyte steatosis obviously increased.NAFLD score was significantly heightened(P<0.01).2)Number of independent activities of rats significantly increased, the serological level of TG, TC, LDL, FBS and FINS were lower significantly after intervention with synbiotics for 2 weeks(P<0.05).3)Synbiotics intervention for two weeks significantly increased the amount of bifidobacterium and lactobacillus and decrease the amount of enterococcus significantly(P<0.05).4)The expression of TLR4 was gradually increased in the process of NASH rats modeling(P<0.05),but decreased after 2 weeks of the synbiotics-intervention (P<0.05).Conclusions Intestinal microecology change is closely related to the development of NASH,therefor, synbiotics could improve the quality of life and biochemical indicators of NASH rats through adjusting intestinal microecology and the expression level of TLR4 protein might been involved.
ABSTRACT
Objective To study the effects of endoplasmic reticulum stress on liver damage in young rats fed with high-fat diet.Methods We divided 48 male weaned young rats randomly into high-fat diet group and control group,which were separately fed with high-fat diet and normal diet.After feeding 8,12 and 1 6 weeks,the body weight and visceral fat of the rats were measured.The serum liver function was measured.The morphology of livers was observed by HE and transmission electron microscopy. The mRNA expressions of ATF6 and GRP78 in hepatocytes were measured with RT-PCR.Results ① The body weight and visceral fat weight of rats in high-fat diet group increased compared with those in control group (P 0.05);alanine aminotransferase at week 1 6 was increased significantly compared with that in controls (P < 0.05 ).③ Liver cells in high-fat diet group had steatosis at week 8 and the steatosis became more serious between week 12 and week 1 6.④ In high-fat diet group at week 8 there were a large number of lipid droplets in the cytoplasm,and the cell structure was close to that of normal cells;rough endoplasmic reticulum was nearly normal and the ribosome was visible.At week 12 and week 1 6,besides a large number of lipid droplets,we could also see that some substances with line-like structure deposited in rough endoplasmic reticulum pool.⑤ The expressions of ATF6 and GRP78 mRNA in hepatocytes in high-fat group at weeks 8, 12 and 1 6 were significantly increased compared with those in control group (P <0.05). Conclusion High-fat diet in infants can cause visceral fat accumulation,fatty degeneration of hepatocytes and liver injury.ATF6-mediated endoplasmic reticulum may be closely related to the liver injury which results from highfat diet.
ABSTRACT
Objective: To detect and compare serum lipid abnormalities in patients diagnosed with different grades of non-alcoholic fatty liver on ultrasonography.Methods:A total of 70 cases which included 30 males and 40 females, diagnosed as non-alcoholic fatty liver disease (NAFLD) on ultrasound were investigated with serum lipid profile. Then a comparison of lipid abnormalities between different grades of fatty liver diagnosed on ultrasound was done. P value was calculated by using analysis of variance test (ANOVA) and P value <0.05 was considered as statistically significant.Results:Out of 70 cases which were diagnosed as NAFLD cases were 47.15%, grade II were 42.85% and grade III were 10%. The mean age of the patients was 49.14 years. Male to female ratio was 3:4. Serum triglycerides, total cholesterol, LDL and VLDL levels were raised in 67.14%, 45.71% 34.28%, 25.71% of cases respectively. Low serum HDL levels were seen in 62.85% of patients. On statistical analysis we found increasing grades of NAFLD were significantly associated with increasing values of total cholesterol (P value-0.001), LDL (P value-0.000) and VLDL (P value-0.003) and decreasing HDL (P value-0.000).Conclusion:Most of the patients of NAFLD in India is asymptomatic, non-diabetic and on ultrasonography, grade I NAFLD non-hypertensive. Though liver biopsy is the gold standard method for diagnosis of NAFLD, Ultrasonography which is non-invasive, simple tool, can be used for the early detection of NAFLD in asymptomatic patients.
ABSTRACT
No abstract available.
Subject(s)
Aged , Female , Humans , Fatty Liver/epidemiology , Hepatitis/epidemiology , Insulin Resistance , Metabolic Syndrome/complications , Prevalence , Prognosis , Risk FactorsABSTRACT
@#ObjectiveTo investigate the role of serine/threonine kinase (Akt) and lipoprotein lipase (Lpl) in formation of nonalcoholic steatohepatitis (NASH) in rat with a fat-rich diet.Methods40 male Wistar rats were randomly divided into the 8-week-rich-fat group (n=10), 8-week-common-diet control group (n=10), 12-week-rich-fat group (n=10) and 12-week-common-diet control group (n=10). The lipid, cholesterol, glucose and insulin were examined, insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated, the expression of Akt and Lpl were detected with immunohistochemical method and morphological changes of liver were observed by transmission electron microscope (TEM).ResultsNASH was formed in each rat of 8-week-rich-fat group with characteristics of individual obese, increased liver volume, full and clear contour, gray-yellowish luster, greasy section and crisp quality. And it was accompanied by high lipoidemia (HL), liver fat cell denaturation, inflammatory cell infiltration in liver lobuler and cell death in liver. The expression of Akt was obviously reduced and the expression of Lpl was obviously weakened in liver. Lipid, cholesterol, glucose and insulin and IRI were gradually advancing. ISI was reducing and the insulin resistance formed. The data of fat-rich diet groups was significantly different with that of common-diet control groups (P<0.0001).Conclusion Steatohepatitis and insulin resistance can form in rat by feeding with rich-fat diet for 8 weeks. It causes the insulin and Lpl activeness reducing, and steatolysis barrier.
ABSTRACT
BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, obesity, and insulin resistance, which are the main features of metabolic syndrome. First, we examined the prevalence of metabolic syndrome among patients with NAFLD. We then compared the prevalence of metabolic syndrome in simple steatosis with that in nonalcoholic steatohepatitis (NASH). Finally, we sought to identify clinical factors associated with the stage of liver fibrosis. METHODS: From November 2002 to March 2004, we enrolled consecutive 25 patients with NAFLD from patients visiting outpatient clinic. The 17 controls were healthy persons who visited our health promotion center. We compared the clinical and biochemical data of the NAFLD group with those of the control group. Using histologic findings, we divided NAFLD into simple steatosis and NASH. We then compared the clinical and biochemical data of the simple steatosis group with those of the NASH group. RESULTS: Fourteen patients (14/25, 56%) had metabolic syndrome in the NAFLD group. There was no difference in the prevalence of metabolic syndrome between the simple steatosis (5/10, 50%) and the NASH group (9/15, 60%). We found significant differences in cardiovascular risk factors between the two groups, but homeostasis model assessment insulin resistance was the only significantly different factor between the simple steatosis group and the NASH group. In addition, no difference in histological features was found between NASH with metabolic syndrome and without metabolic syndrome. CONCLUSIONS: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. We could not find any cardiovascular risk factors that could predict a severe fibrosis.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , English Abstract , Fatty Liver/complications , Metabolic Syndrome/complicationsABSTRACT
Objective To establish the diagnosis criterion and management protocol for nonalcoholic steatohepatitis(NASH).Methods The data of 75 patients with NASH including 10 chronic hepatitis,10 simple fatty,15 alcoholic liver disease,10 healthy conerol and 40 tpye 2 diabetic patient without viral hepatitis were investigated.Results Among 75 NASH patients,the mean age was 36.8 years,and male were 66(88%);their body mass index(BMI)≥25 were 58 (77.3%).Serum ALT and insulin concentration were elevated in all patients with NASH;60 cases were with hypertriceridemia (80%),30 with normal oral glucose tolerate test (OGTT) (40%),fatty liver was detected in 67 patients (90%)by ultrasonography.The BMI were different between NASH and healthy controls,P